Publications by authors named "Al-Ola Abdallah"

36 Publications

A Systematic Review and Network Meta-analysis of Randomized Data on Efficacy of Novel Therapy Combinations in Patients with Lenalidomide-refractory Multiple Myeloma.

Clin Lymphoma Myeloma Leuk 2021 Mar 26. Epub 2021 Mar 26.

Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS.

Introduction: Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most important clinical questions in its treatment. Given the lack of direct comparisons of treatment regimens for lenalidomide-refractory MM, we used a systematic review to identify randomized controlled trials (RCTs) that included lenalidomide-refractory subgroup analysis.

Methods: We performed a systematic review to identify RCTs for MM that enrolled patients with lenalidomide-refractory disease, then performed a network meta-analysis (NMA) using random effects model to compare regimens.

Results: We identified 123 discrete RCTs, of which 7 reported primary outcomes for lenalidomide-refractory MM. These were linked in 2 discrete networks totaling 1698 lenalidomide-refractory patients. Network 1 compared bortezomib (bort)/dexamethasone (dex) versus other treatments, and analysis showed triplet therapy with pomalidomide (pom)/bort/dex (hazard ratios [HR] 0.65, 95% confidence interval [CI], 0.50-0.84), daratumumab (dara)/bort/dex (HR 0.36, 95% CI, 0.21-0.63), and dara/carfilzomib (carf)/dex (HR 0.38, 95% CI, 0.21-0.69) as more effective than bort/dex. Network 2 compared dex versus other treatments, and analysis showed pom/dex (HR 0.50, 95% CI, 0.40-0.62), isatuximab (isa)/pom/dex (HR 0.30, 95% CI, 0.20-0.44), and elotuzumab (elo)/pom/dex (HR 0.27, 95% CI, 0.16-0.45) as more effective than dex. Within each network, monoclonal antibody (mAb)-containing regimens had lower HRs and higher P-scores than non-mAb regimens, indicating higher likelihood of these regimens being most efficacious.

Conclusion: The results of our NMA demonstrated that for lenalidomide-refractory MM, triplet therapy containing mAbs are superior. There is need for further RCTs to better ascertain the best standard of care for these patients.
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http://dx.doi.org/10.1016/j.clml.2021.03.006DOI Listing
March 2021

Multiple myeloma triplet therapies: baseline characteristics and control groups.

Lancet 2021 May;397(10285):1620-1621

Division of Hematology and Division of Medical Oncology, University of California San Francisco, San Francisco, CA, USA.

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http://dx.doi.org/10.1016/S0140-6736(21)00274-9DOI Listing
May 2021

Reporting of Postprotocol Therapies and Attrition in Multiple Myeloma Randomized Clinical Trials: A Systematic Review.

JAMA Netw Open 2021 Apr 1;4(4):e218084. Epub 2021 Apr 1.

Divisions of Hematology & Medical Oncology, University of California, San Francisco.

Importance: A thorough understanding of the optimal role and sequence of agents for treatment of multiple myeloma (MM) requires knowledge of the use and rate of postprotocol therapies in randomized clinical trials (RCTs).

Objectives: To examine the proportion of MM RCTs that reported postprotocol therapies and, among those, the percentage of patients who received no further therapy and how treatments differed between the control and intervention arms.

Evidence Review: The reporting of postprotocol therapies was systematically assessed in published MM RCTs using 3 databases (PubMed, Embase, and Cochrane Registry of Controlled Trials) for MM RCTs from January 1, 2005, to December 30, 2019. All MM RCTs were included, and all other studies, such as editorials, nonrandomized studies, and review articles, were excluded.

Findings: A total of 103 RCTs were identified (47 251 patients); of these, 45 (43.7%) reported subsequent treatments in that publication or in any subsequent publication. Trials funded by pharmaceutical companies (26 of 47 [55.3%]) were more likely to report subsequent treatments than cooperative group studies (19 of 56 [33.9%]) (χ21,103 = 4.8; P = .03). Differences were found in the treatments received between the intervention and control arms of RCTs. When data were reported, 5150 of 9351 patients (54.9%) in RCTs of newly diagnosed MM and 2197 of 4501 patients (48.8%) in RCTs of relapsed/refractory MM received any subsequent therapy.

Conclusions And Relevance: Postprotocol therapies in MM RCTs are often not reported and, when they are, many patients receive no further therapy. Reporting guidelines for postprotocol therapies are needed.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082314PMC
April 2021

Hospitalization at the end of life in patients with multiple myeloma.

BMC Cancer 2021 Mar 31;21(1):339. Epub 2021 Mar 31.

Department of Hematological Malignancies and Cellular Therapeutics, Kansas University Medical Center, Kansas City, USA.

Background: Despite advances in treatment, multiple myeloma (MM) remains incurable and results in significant morbidity and mortality. Further research investigating where MM patients die and characterization of end-of-life hospitalizations is needed.

Methods: We utilized the National Inpatient Sample (NIS) to explore the hospitalization burden of MM patients at the end of their lives.

Results: The percent of patients dying in the hospital as a percent of overall MM deaths ranged from 54% in 2002 to 41.4% in 2017 (p < 0.01). Blood transfusions were received in 32.7% of these hospitalizations and infections were present in 47.8% of patients. Palliative care and/or hospice consultations ranged from 5.3% in 2002 to 31.4% in 2017 (p < 0.01).

Conclusion: Our study demonstrates that patients with MM dying in the hospital have a significant requirement for blood transfusions and have a high infection burden. We also show that palliative care and hospice involvement at the end of life has increased over time but remains low, and that ultimately, inpatient mortality has decreased over time, but MM patients die in the hospital at a higher rate than the general population.
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http://dx.doi.org/10.1186/s12885-021-08079-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011131PMC
March 2021

Quality of control groups in randomised trials of multiple myeloma enrolling in the USA: a systematic review.

Lancet Haematol 2021 Apr;8(4):e299-e304

Divisions of Hematology and Medical Oncology, University of California San Francisco, San Francisco, CA, USA.

To our knowledge, no study has evaluated the quality of control groups in randomised controlled trials of multiple myeloma. We aimed to do a systematic review of randomised controlled trials of multiple myeloma to ascertain the quality of the control groups used. PubMed (MEDLINE), Embase, Cochrane Controlled Register of Trials, and CinicalTrials.gov were searched for articles of randomised controlled trials of multiple myeloma based in the USA that initiated participant enrolment between Jan 1, 2010, and June 30, 2020. A control group regimen was considered to be inferior if a previous randomised controlled trial had shown an improved progression-free survival versus the control group before enrolment. Of 49 identified randomised controlled trials, seven (14%) began enrolling patients into inferior control groups after an existing superior regimen to the control had already been published. Nine (18%) of the 49 trials continued enrolment on substandard control groups after data emerged during the study enrolment period. The median time that newer data emerged regarding inferiority of the control group from the time a trial first enrolled a patient was 13 months (IQR 8-29 months). 12 (75%) of these 16 randomised controlled trials are published, and nine (75%) of the 12 published trials had overlapping investigators with trials that had previously shown the inferiority of the control group being used. Greater scrutiny on the quality of control groups in randomised controlled trials of multiple myeloma is needed.
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http://dx.doi.org/10.1016/S2352-3026(21)00024-7DOI Listing
April 2021

Use of endpoints in multiple myeloma randomized controlled trials over the last 15 years: A systematic review.

Am J Hematol 2021 06 1;96(6):690-697. Epub 2021 Apr 1.

Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah, USA.

Surrogate endpoints are being used more frequently in randomized controlled trials, even though they do not consistently corelate with patient outcomes. We systemically evaluated the use of surrogate endpoints in multiple myeloma randomized controlled trials over the past 15 years. We searched three databases (Pubmed, Embase, Cochrane) for multiple myeloma randomized controlled trials from January 1, 2005 to December 30, 2019. The primary outcome of our study was the proportion of randomized controlled trials that used overall survival as their primary endpoint. Secondary outcomes included the use of surrogate endpoints, and trends over time, and whether they differed based on study sponsorship. We included 151 randomized controlled trials in our analysis. The primary endpoint was overall survival (OS) in 17 (11.3%) of studies, progression free survival (PFS) or event-defined endpoints in 91 studies (60.3%) and response-based endpoints in 44 studies (29.1%). Quality of life was a primary endpoint in only three studies (2%). The use of OS as a primary endpoint decreased from 28.5% of trials from 2005 to 2009 to 5.5% from 2015 to 2019. There has been a decrease in the clinically meaningful endpoint of OS over the past 15 years in multiple myeloma randomized controlled trials. Use of quality of life as a primary endpoint remains exceedingly low. It remains paramount to recognize that the use of surrogate endpoints is imperfect, and care based upon them requires constant physician and patient re-analysis.
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http://dx.doi.org/10.1002/ajh.26166DOI Listing
June 2021

Caution With Routine Use of Daratumumab for Newly Diagnosed High-Risk Multiple Myeloma.

JAMA Oncol 2021 Apr;7(4):635

Division of Hematology & Hematologic Malignancies, Department of Internal Medicine, University of Utah, Salt Lake City.

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http://dx.doi.org/10.1001/jamaoncol.2020.8008DOI Listing
April 2021

Renal insufficiency in multiple myeloma: a systematic review and meta-analysis of all randomized trials from 2005-2019.

Leuk Lymphoma 2021 Jun 8;62(6):1386-1395. Epub 2021 Jan 8.

Department of Hematology and Oncology, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA.

Clinical trials may be inconsistent in their enrollment and reporting of patients with multiple myeloma (MM) who have renal insufficiency (RI). We performed a systematic review of all MM randomized clinical trials (RCT) from 2005-2019 to evaluate reporting of prevalence, eligibility criteria and outcomes of patients with RI and MM. One-hundred and twenty-three RCTs were included. Only 30% of studies clearly reported on the proportion of patients who had RI. Only 68.2% reported eligibility criteria pertaining to RI, with no uniformity in the reported criteria. The relative risk (RR) of disease progression or death in patients with RI was higher than those without, RR of 1.20 (1.003-1.431) for relapsed/refractory and 1.07 (1.001-1.046) for newly diagnosed. There is inconsistent reporting and enrollment of patients with RI on MM RCT's. We advocate for higher enrollment of patients with RI and transparent reporting of their eligibility criteria and outcomes.
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http://dx.doi.org/10.1080/10428194.2020.1867725DOI Listing
June 2021

Maintenance regimens after a second autologous transplant for multiple myeloma.

Leuk Lymphoma 2021 03 4;62(3):758-760. Epub 2020 Nov 4.

Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.

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http://dx.doi.org/10.1080/10428194.2020.1842402DOI Listing
March 2021

Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study.

Blood Cancer J 2020 10 23;10(10):106. Epub 2020 Oct 23.

Emory University, Winship Cancer Institute, Atlanta, GA, USA.

DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3-72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8-not reached [NR]); median progression-free survival was 5.7 months (2.2-9.7); median overall survival was not reached (8.7 months-NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.
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http://dx.doi.org/10.1038/s41408-020-00369-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584571PMC
October 2020

Outcomes of VD-PACE With Immunomodulatory Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma.

Clin Lymphoma Myeloma Leuk 2021 Feb 30;21(2):e220-e226. Epub 2020 Sep 30.

Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS.

Background: Aggressive relapsed/refractory multiple myeloma (RRMM) often requires salvage cytotoxic chemotherapy. We evaluated the efficacy and toxicity of VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) with an immunomodulatory agent (IMiD) in RRMM.

Patients And Methods: We retrospectively reviewed the effectiveness and tolerability among 30 patients with RRMM receiving ≥ 1 cycle of VD-PACE + IMiD between January 2012 to April 2019.

Results: Of 30 patients, 26 (86%) had myeloma double refractory to protease inhibitors and IMiDs, and had received a median of 3 lines prior of therapy. The overall response rate was 67.7%, 13% patients experienced complete remission or better, and 13% experienced very good partial response. Median progression-free and median overall survival were 11 and 26 months, respectively. The most common grade 3 or higher adverse events were hematologic events, which were manageable.

Conclusion: VD-PACE + IMiD is an effective and tolerable salvage treatment for RRMM, with an impressive response rate in pretreated RRMM.
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http://dx.doi.org/10.1016/j.clml.2020.09.002DOI Listing
February 2021

Outcomes of Daratumumab, Pomalidomide, and Dexamethasone, Followed by High-dose Chemotherapy and Autologous Stem Cell Transplantation, in Patients With Relapsed/Refractory Multiple Myeloma.

Clin Lymphoma Myeloma Leuk 2021 Feb 18;21(2):e212-e219. Epub 2020 Sep 18.

Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS.

Background: The number of therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) has increased significantly. Our institute treated a series of patients with RRMM using DPd (daratumumab, pomalidomide, dexamethasone) as salvage therapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT).

Patients And Methods: We treated 18 patients with RRMM from May 2016 to April 2020, with DPd as salvage therapy, followed by HDCT and ASCT. DPd was administered as daratumumab 16 mg/kg weekly for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and then every 4 weeks. Pomalidomide was given at 4 mg orally on days 1 to 21 of a 28-day cycle, and dexamethasone at 20 or 40 mg weekly.

Results: The patients had received a median of 2 (range, 1-4) previous regimens. Of the 18 patients, 13 (72%) had received ASCT before this treatment. In addition, 78% had disease refractory to proteasome inhibitors, 78% refractory to immunomodulatory agents, and 72% double refractory to immunomodulatory agents and proteasome inhibitors. The overall response rate after salvage treatment with DPd was 100% and at day 100 after ASCT was 100%; 67% had achieved a complete response or better and 78% had achieved a very good partial response or better. No treatment-related mortality had occurred by day 100. The 2-year progression-free and overall survival rates were 83.3% and 94.4%, respectively. The most common grade ≥ 3 adverse events were thrombocytopenia (100%), neutropenia (100%), and neutropenic fever (67%).

Conclusions: DPd as salvage therapy, followed by HDCT and ASCT, demonstrated deep, durable, and clinically meaningful responses with a manageable safety profile in patients with RRMM.
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http://dx.doi.org/10.1016/j.clml.2020.08.026DOI Listing
February 2021

Inpatient mortality of patients with multiple myeloma and renal impairment undergoing autologous stem cell transplantation.

Eur J Haematol 2020 Nov 5;105(5):571-577. Epub 2020 Aug 5.

Department of Hematological Malignancies and Cellular Therapeutics, University of Kansas, Kansas City, KS, USA.

Objectives: Further data are needed on the safety of high-dose melphalan and autologous stem cell transplant (HDM-ASCT) in patients with multiple myeloma (MM) and renal impairment. The objective of our study was to use the National Inpatient Sample (NIS) to determine inpatient mortality for patients with MM and renal impairment undergoing HDM-ASCT, as well as trends over time.

Methods: Using the NIS, we tracked hospital admissions for MM patients from 2002 to 2014 who underwent HDM-ASCT, using ICD 9 coding.

Results: The total weighted estimate of inpatient admissions for HDM-ASCT among MM patients was 47,253 from 2002 to 2014. A weighted total of 45 and 1709 patients with MM received peritoneal dialysis (PD) and hemodialysis (HD) during HDM-ASCT for MM, respectively. There was a markedly increased risk of inpatient mortality in patients on dialysis undergoing transplant (20.5% for PD patients, 13.8% for HD patients), even after accounting for other comorbidities (odds ratio of inpatient mortality of 6.193 [CI 3.585-10.701]). A significant decrease was noted in inpatient mortality for patients with ESRD undergoing HDM-ASCT over time from 15.6% in 2009 to 5% in 2014 (P < .001).

Conclusion: Patients with MM on dialysis undergoing HDM-ASCT are at significantly increased risk of inpatient mortality.
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http://dx.doi.org/10.1111/ejh.13487DOI Listing
November 2020

CAR-T treatment for hematological malignancies.

J Investig Med 2020 06 21;68(5):956-964. Epub 2020 Mar 21.

Department of Internal Medicine, Division of Hematological Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.

Chimeric antigen receptor (CAR)-T-cell therapy has sparked a wave of optimism in hematological malignancies, reflected by the successful results of early clinical trials involving patients with pre-B-cell acute lymphoblastic leukemia, B-cell lymphomas and multiple myeloma. CAR-T-cell therapy is considered to be a novel immunotherapy treatment that has the potential for curing certain hematological cancers. However, as use of CAR-T-cell therapy has grown, new challenges have surfaced. These challenges include the process of manufacturing the CAR-T cells, the mechanisms of resistance that underlie disease relapse, adverse effects and cost. This review describes the published results of clinical trials and expected developments to overcome CAR-T resistance.
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http://dx.doi.org/10.1136/jim-2020-001290DOI Listing
June 2020

Health Care Reimbursement, Service Utilization, and Outcomes among Medicare Beneficiaries with Multiple Myeloma Receiving Autologous Hematopoietic Cell Transplantation in Inpatient and Outpatient Settings.

Biol Blood Marrow Transplant 2020 04 7;26(4):805-813. Epub 2020 Jan 7.

University of Kansas Medical Center, Westwood, Kansas.

Autologous hematopoietic stem cell transplantation (auto-HCT) is a complex procedure that can be performed in both inpatient (IP) and outpatient (OP) care settings. We examined reimbursement, service utilization, and patient financial responsibility among Medicare beneficiaries with multiple myeloma who underwent auto-HCT in the IP and OP settings using a merged dataset of the Center for International Blood and Marrow Transplant Research observational database and Centers for Medicare & Medicaid Services Medicare administrative claims data. Selection criteria included first auto-HCT, time from diagnosis to auto-HCT <18 months, and continuous enrollment in Medicare Parts A and B for 30 days before HCT index claims and 100 days post-HCT or until death. Total reimbursement and patient responsibility were adjusted for patient and disease characteristics using a weighted generalized linear model. The final cohort comprised 1640 patients, 1445 (88%) who received IP-HCT and 195 (12%) who received OP-HCT. The adjusted total mean reimbursement was higher for IP-HCT compared with OP-HCT ($82,368 [95% CI, $77,643 to $87,381] versus $46,824 [95% CI, $43,567-$50,325]; P < .0001). Adjusted total mean patient responsibility was $4736 for IP-HCT (95% CI, $4731 to $5133) and $6944 for OP-HCT (95% CI, $6296 to $7658) (P < .0001). Within 100 days post-HCT, 107 of the 195 OP-HCT recipients (55%) had at least 1 subsequent admission, compared with 348 of the 1445 IP-HCT recipients (24%). Reimbursement, service utilization, and financial responsibility varied by HCT setting. As the number of Medicare beneficiaries who undergo auto-HCT increases, coverage policy needs to consider how location of services leads to variations in the financial burden for both hospital systems and patients.
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http://dx.doi.org/10.1016/j.bbmt.2019.12.772DOI Listing
April 2020

Antibiotic prophylaxis for patients with newly diagnosed multiple myeloma: Systematic review and meta-analysis.

Eur J Haematol 2020 May 22;104(5):420-426. Epub 2020 Feb 22.

Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, MD Anderson Cancer Center, Houston, Texas.

Objective: Ascertain the benefit of prophylactic antibiotics for patients with newly diagnosed multiple myeloma (MM), given that clinical trials evaluating this have had conflicting results.

Methods: We performed a systematic review and meta-analysis evaluating the use of prophylactic antibiotics in patients with MM and its impact on infection risk and mortality.

Results: Across three included studies, a total of 664 patients received antibiotics and 650 patients received no antibiotics. The overall incidence of infection within 3 months was lower for antibiotic group compared to placebo (18.4% vs 23.4%, RR: 0.79, 95% CI 0.62-1.00, P = .05, I  = 6.5%). There was no difference in mortality in the first 3 months (1.5% vs 3.5%, RR: 0.47, 95% CI 0.17-1.27, P = .60, I  = 28.1%).

Conclusion: Antibiotic prophylaxis for a finite duration can decrease the overall incidence of infection within the first 3 months following diagnosis. This does not lead to a decrease in mortality. Further data on antibiotic resistance patterns, toxicity, healthcare expenditures, and the impact of antibiotics on subsequent therapies can assist providers in helping make decisions on prophylactic antibiotics with their patients.
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http://dx.doi.org/10.1111/ejh.13374DOI Listing
May 2020

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study.

Lancet Oncol 2020 02 16;21(2):207-221. Epub 2019 Dec 16.

GlaxoSmithKline, Philadelphia, PA, USA.

Background: Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study.

Methods: DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with relapsed or refractory multiple myeloma with disease progression after three or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody with an Eastern Cooperative Oncology Group performance status of 0-2 were recruited, centrally randomly assigned (1:1) with permuted blocks (block size 4), and stratified by previous lines of therapy (≤4 vs >4) and cytogenetic features to receive 2·5 mg/kg or 3·4 mg/kg belantamab mafodotin via intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. The intention-to-treat population comprised all randomised patients, regardless of treatment administration. The safety population comprised all patients who received at least one dose of belantamab mafodotin. The primary outcome was the proportion of randomly assigned patients in the intention-to-treat population who achieved an overall response, as assessed by an independent review committee. This study is registered with ClinicalTrials.gov, NCT03525678, and is ongoing.

Findings: Between June 18, 2018, and Jan 2, 2019, 293 patients were screened and 196 were included in the intention-to-treat population (97 in the 2·5 mg/kg cohort and 99 in the 3·4 mg/kg cohort). As of June 21, 2019 (the primary analysis data cutoff date), 30 (31%; 97·5% CI 20·8-42·6) of 97 patients in the 2·5 mg/kg cohort and 34 (34%; 23·9-46·0) of 99 patients in the 3·4 mg/kg cohort achieved an overall response. The most common grade 3-4 adverse events in the safety population were keratopathy (in 26 [27%] of 95 patients in the 2·5 mg/kg cohort and 21 [21%] of 99 patients in the 3·4 mg/kg cohort), thrombocytopenia (19 [20%] and 33 [33%]), and anaemia (19 [20%] and 25 [25%]); 38 (40%) of 95 patients in the 2·5 mg/kg cohort and 47 (47%) of 99 in the 3·4 mg/kg cohort reported serious adverse events. Two deaths were potentially treatment related (one case of sepsis in the 2·5 mg/kg cohort and one case of haemophagocytic lymphohistiocytosis in the 3·4 mg/kg cohort).

Interpretation: Single-agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma.

Funding: GlaxoSmithKline.
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http://dx.doi.org/10.1016/S1470-2045(19)30788-0DOI Listing
February 2020

Outcomes of autologous stem cell transplant for cardiac AL-amyloidosis and cardiac light chain deposition disease.

J Oncol Pharm Pract 2020 Jul 3;26(5):1128-1133. Epub 2019 Dec 3.

Department of Hematology Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, NC, USA.

Introduction: Cardiac amyloidosis and light chain deposition disease (LCDD) are the most common cause of death in AL amyloidosis or LCDD.

Methods: Our multiple myeloma database identified 50 patients with cardiac amyloidosis or LCDD between January 2004 and January 2013. Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes.

Results: The median age at diagnosis was 61 years for those who received autologous hematopoietic stem cell transplant (ASCT) and 71 years for those who received only bortezomib-based chemotherapy; 62.5% (n = 30) of patients had elevated levels of NT-proBNP ≥323 ng/L, and 29.2% (n = 14) of patients had an elevated cTnT ≥0.1 µg/L. Echocardiogram findings showed a speckled appearance in 18% (n = 9) of patients, and 60% (n = 30) of patients had an increased diastolic intra-ventricular septum (IVSD) thickness measuring ≥1.3 cm; 64.3% (n = 18) of patients who underwent cardiac MRI showed subendocardial enhancement. Out of 48 patients who received treatment, 37 patients were diagnosed with cardiac amyloidosis and 11 patients were diagnosed with cardiac LCDD. Twenty-eight patients (75.7%) with cardiac amyloidosis received ASCT, compared to 34.3% (n = 9) patients who were ineligible for ASCT and received chemotherapy only. Patients who underwent ASCT had a median OS of 4.48 years compared to 1.82 years (p = 0.69) for those receiving chemotherapy alone.

Conclusion: Our single institution experience shows that ASCT is feasible for cardiac amyloidosis and/or cardiac LCDD. However, careful selection of proper patients and diligent supportive care are vital to decreasing transplant-related mortality.
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http://dx.doi.org/10.1177/1078155219888564DOI Listing
July 2020

A novel prostate cancer immunotherapy using prostate-specific antigen peptides and skin test reagent as an adjuvant.

SAGE Open Med 2018 17;6:2050312118800202. Epub 2018 Sep 17.

Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Objectives: Our group developed the use of the skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate cancer immunotherapy.

Methods: Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate cancer patients using interferon-γ enzyme-linked immunospot assay.

Results: The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides.

Conclusion: In summary, a design and a formulation of a novel prostate cancer immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate cancer patients supports further development of this immunotherapy.
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http://dx.doi.org/10.1177/2050312118800202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144584PMC
September 2018

Clinical Presentation and Gene Expression Profiling of Immunoglobulin M Multiple Myeloma Compared With Other Myeloma Subtypes and Waldenström Macroglobulinemia.

J Glob Oncol 2018 09 9;4:1-8. Epub 2017 May 9.

Shebli Atrash, Qing Zhang, Xenofon Papanikolaou, Caleb Stein, Al-Ola Abdallah, and Bart Barlogie, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Qing Zhang, Levine Cancer Institute, Charlotte, NC.

Purpose: Multiple myeloma (MM) is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated postgerminal B cells. It is a heterogeneous disease both at the genetic level and in terms of clinical outcome. Immunoglobulin M (IgM) MM is a rare subtype of myeloma. Similar to Waldenström macroglobulinemia (WM), patients with MM experience IgM monoclonal gammopathy; however, both diseases are distinct in terms of treatment and clinical behavior.

Materials And Methods: To shed light on the presentation of IgM MM, its prognosis, and its gene expression profiling, we identified and characterized 21 patients with IgM MM from our database.

Results: One of these patients presented with a rare IgM monoclonal gammopathy of undetermined significance that progressed to smoldering myeloma. The median survival of the 21 patients was 4.9 years, which was comparable to a matched group of patients with non-IgM MM with similar myeloma prognostic factors (age, gender, albumin, creatinine, anemia, lactate dehydrogenase, β-microglobulin, cytogenetics abnormalities), but much less than the median survival reported for patients with WM (9 years). We identified a cluster of genes that differ in their expression profile between MM and WM and found that the patients with IgM MM displayed a gene expression profile most similar to patients with non-IgM MM, confirming that IgM MM is a subtype of MM that should be differentiated from WM.

Conclusion: Because the prognosis of IgM MM and WM differ significantly, an accurate diagnosis is essential. Our gene expression model can assist with the differential diagnosis in controversial cases.
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http://dx.doi.org/10.1200/JGO.2016.008003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180798PMC
September 2018

Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years.

Hematology 2018 Jan 2;23(1):17-24. Epub 2017 Jun 2.

b Division of Hematology and Oncology , Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences , Little Rock , AR , USA.

Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.

Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.

Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002-2015).

Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n = 19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n = 12), 35% for CD68 (n = 8), 30% for CD34 (n = 7), and 26% for lysozyme (n = 6). Cytogenetic abnormalities were seen in 63% (n = 12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n = 3) or monosomal (n = 2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4-24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p = 0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p < 0.001). All patients who underwent allogeneic hematopoietic stem cell transplant attained long-term remissions, with a median follow-up of 54 (range 32-120) months.

Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.
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http://dx.doi.org/10.1080/10245332.2017.1333275DOI Listing
January 2018

Image Diagnosis: Splenic Infarction Associated with Oral Contraceptive Pills in a Healthy Young Woman.

Perm J 2017 ;21:16-071

Assistant Professor of Medicine in the Division of Hematology and Oncology at the Winthrop P Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences in Little Rock.

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http://dx.doi.org/10.7812/TPP/16-071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424590PMC
June 2018

Image Diagnosis: Zinc-Induced Copper Deficiency Causing Pancytopenia Recognized on Bone Marrow Examination.

Perm J 2017 ;21:16-077

Physician in the Division of Hematology and Oncology for the Winthrop P Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences, and in the Division of Hematology and Oncology for the Central Arkansas Veterans Healthcare System in Little Rock.

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http://dx.doi.org/10.7812/TPP/16-077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283791PMC
September 2017

Improving Communication on Intent of Chemotherapy Using QOPI Scores and PDSA Cycles.

J Cancer Educ 2016 12;31(4):736-741

Division of Hematology and Oncology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Using the standardized ASCO Quality Oncology Practice Initiative (QOPI) guidelines for assessing quality cancer care, we identified communication about intent of chemotherapy as an area needing improvement in our program at the University of Arkansas for Medical Sciences (UAMS) and the Central Arkansas Veterans Healthcare System (CAVHS). We organized training in communications on intent of treatment (palliative vs curative) and added optional checkboxes to our electronic templates for progress notes. Afterwards, we conducted a retrospective review of electronic medical records of initially often randomly selected patient charts. The first 10 patient charts after 1 month of implementation showed intent of treatment in 80 % of charts compared to 74 % at baseline. We then changed checkboxes from mandatory to optional and reviewed 30 randomly selected patient charts. Intent of treatment was documented in 96.7 % of cases compared to 74 % at baseline. We also assessed patient satisfaction through surveys distributed in clinic. Patient satisfaction scores were close to 100 % for receiving clear information, understanding the reason for which they were receiving chemotherapy, and willingness of oncologists to listen carefully, to take time to answer questions, to explain things clearly, and to spend adequate time with them. In this study, we showed that training in communication of intent of chemotherapy and use of checkboxes in progress note templates could improve competency in communication of intent of therapy in cancer patients.
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http://dx.doi.org/10.1007/s13187-015-0897-xDOI Listing
December 2016

Metastatic Renal Cell Carcinoma Presenting as Painful Chewing Successfully Treated with Combined Nivolumab and Sunitinib.

Perm J 2016 27;20(3):15-149. Epub 2016 Jun 27.

Associate Professor of Medicine in the Department of Hematology and Oncology at the University of Arkansas for Medical Sciences in Little Rock.

Introduction: Metastatic renal cell carcinoma (RCC) to the head and neck is rare. It is the third-most common cause of distant metastasis to the head and neck, after breast cancer and lung cancer. Several drugs are available to treat metastatic RCC including high-dose interleukin and targeted therapy. Immunotherapy with nivolumab was recently approved by the US Food and Drug Administration (FDA) as a second-line treatment for patients with metastatic RCC.

Case Presentation: We present a case of metastatic RCC in a 71-year-old man with a single complaint of a 1-year history of pain while chewing food. Positron emission tomography-computed tomography showed diffuse metastatic disease. Nivolumab, off-label use before its recent FDA approval, was combined with sunitinib and resulted in an excellent and ongoing response.

Discussion: RCC is the third-most common cause of distant metastasis to the head and neck. The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease. The other important aspect of this case is the almost complete response of his metastatic disease to the combination of nivolumab and sunitinib that was used off label before the FDA issued the approval. Future clinical trials should look at combining immunotherapy with targeted therapy in metastatic RCC.
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http://dx.doi.org/10.7812/TPP/15-149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991901PMC
April 2017

Pazopanib- and bevacizumab-induced reversible heart failure in a patient with metastatic renal cell carcinoma: A case report.

J Oncol Pharm Pract 2016 Jun 7;22(3):561-5. Epub 2015 May 7.

Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, Arkansas, USA Department of Internal Medicine, Division of Hematology and Oncology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA

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http://dx.doi.org/10.1177/1078155215585189DOI Listing
June 2016

MYC amplification in multiple marker chromosomes and EZH2 microdeletion in a man with acute myeloid leukemia.

Cancer Genet 2015 Mar 7;208(3):96-100. Epub 2015 Feb 7.

Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Pathology and Laboratory Medicine Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.

The role of MYC and EZH2 in acute myeloid leukemia (AML) pathogenesis is poorly understood. Herein we present a case of AML with MYC amplification in marker chromosomes and a microdeletion of chromosome 7 below cytogenetic resolution. The karyotype of the patient's bone marrow aspirate showed three to five marker chromosomes in all dividing cells without other structural or numerical chromosomal abnormalities. Analysis by fluorescence in situ hybridization (FISH) with a probe specific for the human MYC gene revealed amplification of the oncogene localized to the marker chromosomes. Using whole genome single nucleotide polymorphism (SNP) microarray analysis, an approximately 4.4 Mb amplicon containing the MYC gene was identified with an estimated amplification of about 30 copies per leukemic cell and, thus, an average of about 8 copies per marker chromosome. A 6.4 Mb hemizygous microdeletion of chromosome 7 within band q36.1 was also found by SNP microarray analysis in a cellular-equivalent dosage of 50%. The microdeletion spans multiple genes, including EZH2, a gene with well-known cancer association. No mutation was found in the remaining EZH2 allele by next generation gene sequencing. The combination of MYC amplification and EZH2 deletion, which has not been described previously in AML, may suggest a synergistic role of the two oncogenes in the pathogenesis of the patient's acute leukemia.
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http://dx.doi.org/10.1016/j.cancergen.2015.01.010DOI Listing
March 2015

Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature.

J Oncol Pharm Pract 2016 Jun 23;22(3):537-42. Epub 2015 Feb 23.

Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA

Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are published. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab-induced progressive necrotic myelopathy.
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http://dx.doi.org/10.1177/1078155215572932DOI Listing
June 2016

A unique presentation of unilateral pleural effusion in a patient with a high-grade plasma cell neoplasm.

Leuk Lymphoma 2015 12;56(10):2989-91. Epub 2015 May 12.

a Division of Hematology and Oncology , Winthrop P. Rockefeller Cancer Institute , Little Rock , AR , USA.

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http://dx.doi.org/10.3109/10428194.2015.1016934DOI Listing
September 2016