Publications by authors named "Davide Nappi"

14 Publications

  • Page 1 of 1

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments.

Front Oncol 2020 17;10:624661. Epub 2021 Feb 17.

Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy.

Immunotherapy is changing the paradigm of multiple myeloma (MM) management and daratumumab is the first-in-class human monoclonal antibody targeting CD38 approved for the treatment of this malignancy. Daratumumab exerts anti-myeloma activity by different mechanisms of action as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), direct apoptosis, and immunomodulation. After GEN501 and SIRIUS trials showed efficacy of daratumumab monotherapy in heavily pretreated relapsed-refractory multiple myeloma (RRMM), in patients with at least two previous line of therapy, two phase III trials demonstrated superior overall response rate (ORR) and progression free survival (PFS) using triplets daratumumab-bortezomib-dexamethasone (DVd) Vd (CASTOR) or daratumumab-lenalidomide-dexamethasone (DRd) Rd (POLLUX) in relapsed-refractory MM patients; so these combinations have been approved and introduced in clinical practice. The ongoing phase III CANDOR is evaluating the triplet daratumumab-carfilzomib-dexamethasone (DKd) Kd whereas phase III APOLLO trial is exploring daratumumab-pomalidomide-dexamethasone (DPd) PD. Many other trials exploring daratumumab combinations in relapsed-refractory MM are ongoing, and they will provide other interesting results. In newly diagnosed transplant-eligible patients, phase III CASSIOPEIA trial found the combination daratumumab-bortezomib-thalidomide-dexamethasone (Dara-VTd) significantly improves stringent Complete Response (sCR) rate and PFS compared with VTD, whereas in the phase II GRIFFIN study, comparing daratumumab-bortezomib-lenalidomide-dexamethasone (Dara-VRD) VRD, sCR rate was significantly higher using quadruplet combination. Many studies are evaluating daratumumab in consolidation and maintenance therapy after autologous stem cell transplantation (ASCT). As regard patients ineligible for ASCT, a great efficacy of daratumumab-containing combinations was reported by the phase III trials ALCYONE and MAIA, exploring daratumumab-bortezomib-melphalan-prednisone (DVMP) VMP and daratumumab-lenalidomide-dexamethasone (DRd) Rd, respectively. These studies provided results never seen before in this setting. The aim of this paper is to critically review the results obtained with regimens containing daratumumab both in relapsed-refractory and in newly diagnosed MM.
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http://dx.doi.org/10.3389/fonc.2020.624661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928404PMC
February 2021

Can early switch to rituximab-bendamustine in a patient with follicular non-Hodgkin lymphoma progressing during R-CHOP be considered frontline treatment?: A case report.

Medicine (Baltimore) 2020 Aug;99(33):e21440

Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola.

Rationale: Follicular non-Hodgkin lymphoma (fNHL) is a neoplasm characterized by an indolent course and chemosensitivity, but also by disease recurrence. Bendamustine is often used as frontline treatment or second line. HEADING DIAGNOSIS:: fNHL.

Patient Concerns: A 63-year-old Caucasian male with diagnosis of fNHL lymphoma underwent to cyclophosphamide, doxorubicin, vincristine, and prednisone associated with rituximab chemoimmunotherapy, during which interim reevaluation showed progressive disease and severe toxicity.

Interventions: Early switch to rituximab-bendamustine.

Outcomes: This regimen was well tolerated, patient compliance was optimal, there were no delays in administration and no infectious episodes. An interim reevaluation after 3 courses revealed that the patient was fit, the blood cell count was normal, and lymphadenopathies and nocturnal sweating had completely regressed. Of note, the PET/CT scan did not show fluorodeoxyglucose pathological uptake, clearly confirming disease regression.

Lessons: Early switching to a bendamustine-rituximab-based scheme, even during conventional chemotherapy, decreases toxicity and reduces the risk of treatment interruption or delay, with favorable effects on overall response and prognosis.
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http://dx.doi.org/10.1097/MD.0000000000021440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437798PMC
August 2020

ABVD vs BEACOPP escalated in advanced-stage Hodgkin's lymphoma: Results from a multicenter European study.

Am J Hematol 2020 09 30;95(9):1030-1037. Epub 2020 Jun 30.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more intensive chemotherapy regimens, escalated BEACOPP (BEACOPPesc) is superior to ABVD for initial disease control and prolonged time-to-relapse. However, this advantage is associated with higher rate of early and late toxicities. As most of these data have been accumulated from clinical trials, a retrospective analysis was conducted in a large database of patients treated outside clinical trials to investigate the advantages and disadvantages of these regimes in a real-world setting. From October 2009 to October 2018, 397 advanced-stage HL patients treated with either ABVD or BEACOPPesc were retrospectively assessed in 7 European cancer centers (2 Austrian and 5 Italian centers). Complete metabolic remission (CMR) by PET was achieved in 76% and 85% of patients in the ABVD and BEACOPPesc groups, respectively (p = .01). Severe adverse events occurred more frequently with BEACOPPesc than ABVD. At a median follow-up of 8 years, 9% of the patients who achieved CMR after BEACOPPesc relapsed compared to 16.6% in the ABVD group (p = .043). No statistical difference in progression free survival (PFS) was observed between the two cohorts overall (p = .11), but there was a trend towards a superior PFS in high-risk patients treated with BEACOPPesc (p = .074). Nevertheless, overall survival was similar between the two groups (p = .94). In conclusion, we confirm that ABVD is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control, the long-term outcome remains similar between the two regimens.
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http://dx.doi.org/10.1002/ajh.25871DOI Listing
September 2020

Combined Oral Fentanyl Citrate and Midazolam as Premedication for Bone Marrow Aspiration and Biopsy in Patients with Hematological Malignancies: A Randomized, Controlled and Patient-Blinded Clinical Trial.

J Clin Med 2020 Feb 1;9(2). Epub 2020 Feb 1.

Hematology, Department of Clinical Medicine and Surgery, AOU Federico II, 80131 Naples, Italy.

Bone marrow aspiration and biopsy (BMAB) is a painful procedure, and the routinely used local infiltration anesthesia (LIA) with lidocaine is unable to provide pain relief during the most uncomfortable phases. The primary endpoint of the present randomized, patient-blinded trial was to evaluate the efficacy of an opioid and benzodiazepine combination plus LIA (sedoanalgesia) in patients undergoing BMAB for hematological malignancies. The secondary endpoint was the safety of the procedure in an outpatient setting. Ancillary assessments were anticipatory anxiety related to pain recall in the event of re-biopsy, and adequacy of bone tissue harvested. Patients were randomly assigned to one of 2 arms to receive either sedoanalgesic placebo plus LIA (standard group) or oral fentanyl citrate 200 μg plus oral midazolam 5 mg plus LIA (combo group) during BMAB. Pre-procedural anxiety and procedural pain were assessed according to the Numerical Rating Scale (NRS: 0-10), dividing the time of the procedure into five intervals (T0, T1, T2a, T2b and T3) and evaluating the degree of discomfort at each time (T) in both groups. One hundred and sixteen patients were eligible for the study. At T2b (time of biopsy) and T3 (time after biopsy), a significantly lower perception of pain was registered in the combo group. Moreover, there were no significant sedoanalgesia-related side-effects. Finally, histological specimens were higher in quality in the combo group. Sedoanalgesia was highly effective in reducing pain during biopsy, diminished anticipatory anxiety in patients undergoing re-biopsy and led to fewer non-diagnostic specimens being harvested.
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http://dx.doi.org/10.3390/jcm9020395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074337PMC
February 2020

Adding hydroxyurea in combination with ruxolitinib improves clinical responses in hyperproliferative forms of myelofibrosis.

Cancer Med 2019 06 17;8(6):2802-2809. Epub 2019 Apr 17.

Department of Medicine and Surgery, Hematology and Hematopoietic Stem Cell Transplant Center, University of Naples Federico II, Naples, Italy.

Ruxolitinib, an orally bioavailable and selective inhibitor of Janus kinase 1 (JAK1) and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea might improve hematological response. This observational multi-center study enrolled 20 adult patients with intermediate- or high-risk primary MF, post- polycythemia vera MF, or postessential thrombocythemia MF with hyperproliferative manifestations of the disease and WBC and/or platelet counts not controlled by ruxolitinib therapy. The patients received treatment with a combination of ruxolitinib and hydroxyurea. A clinical response of any type was obtained in 8 patients (40%) during ruxolitinib monotherapy and in 17 patients (85%) during ruxolitinib-hydroxyurea combination (P = 0.003). After a median duration of 12.4 months of combination therapy, 16/20 patients had a hematological response; 14/17 patients who had started combination therapy to control WBC count and 2/3 who started in order to reduce platelets count. The number of patients requiring ruxolitinib dosage reduction or discontinuations was lower during combination therapy and, at the end of follow-up the median ruxolitinib dose was increased in 50% of patients. In conclusion, the combination of hydroxyurea with ruxolitinib yielded a high clinical response rate and increased ruxolitinib exposure in patients with hyperproliferative forms of MF.
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http://dx.doi.org/10.1002/cam4.2147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558489PMC
June 2019

Pegfilgrastim in primary prophylaxis of febrile neutropenia in elderly patients with hematological malignancies-bendamustine and G-CSF support.

Support Care Cancer 2019 05 23;27(5):1587-1588. Epub 2019 Jan 23.

Hematology - Department of Clinical Medicine and Surgery, Azienda Ospedaliera Universitaria Federico II, Via Pansini 5, 80131, Naples, Italy.

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http://dx.doi.org/10.1007/s00520-019-4651-5DOI Listing
May 2019

Safety and comfort of domestic bortezomib injection in real-life experience.

Support Care Cancer 2018 Sep 24;26(9):3111-3116. Epub 2018 Mar 24.

Hematology, Department of Clinical Medicine and Surgery, University Federico II, Via Pansini 5, 80131, Naples, Italy.

Despite novel agents, multiple myeloma is still an incurable disease, especially for elderly and frail patients, who are difficult to manage for concomitant comorbidities as the therapeutic options are limited and the response to chemotherapy is often short. We report our evaluations upon safety and efficacy of domestic subcutaneous bortezomib in elderly and frail patients candidate to bortezomib-melphalan-prednisone (VMP) regimen. We confirmed that overall incidence of adverse events, including peripheral neuropathy, was low, and in no case required admission to emergency service, contributing to reduce the rate of therapy discontinuation. These results confirm the effectiveness and safety of subcutaneous bortezomib, in a real-life-experience, and define a new possibility of safe auto-administration in a comfortable domestic setting. We suggest that domestic treatment can significantly improve the quality of life of the patients, avoiding unnecessary transfer to the hospital without reducing treatment efficacy.
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http://dx.doi.org/10.1007/s00520-018-4155-8DOI Listing
September 2018

Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience.

Anticancer Drugs 2018 04;29(4):371-372

Departments of Clinical Medicine, Division of Hematology.

Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.
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http://dx.doi.org/10.1097/CAD.0000000000000604DOI Listing
April 2018

Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study.

Oncologist 2018 04 9;23(4):454-460. Epub 2018 Jan 9.

Haematology Division, "Federico II" University Hospital, Naples, Italy.

Background: Rituximab plus bendamustine (R-B) has been demonstrated to improve outcomes and reduce toxicity compared with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) in follicular lymphoma (FL). Nevertheless, in clinical practice, many centers still prefer R-CHOP to R-B in patients with FL grade 3A (FL3A). Therefore, we retrospectively assessed patients with FL3A treated with either R-CHOP or R-B in five European cancer centers and compared their outcomes.

Materials And Methods: We retrospectively assessed 132 patients affected by FL grade 3A treated with either R-B or R-CHOP in the first line and evaluated outcome and toxicity according to the type of treatment. This study included 101 patients who were a subgroup of a previously published cohort.

Results: R-B was less toxic and achieved a similar percentage of complete remissions compared with R-CHOP (97% vs. 96%,  = .3). During follow-up, 10 (16%) patients relapsed after R-B and 29 (41%) after R-CHOP ( = .001), leading to a median progression-free survival (PFS) of 15 versus 11.7 years, respectively ( = .03). Furthermore, R-B overcame the negative prognostic impact of BCL2 expression (15 vs. 4.8 years;  = .001). However, median overall survival was similar between both groups (not reached for both;  = .8).

Conclusion: R-B as a first-line treatment of FL3A is better tolerated than R-CHOP and seems to induce more profound responses, leading to a significantly lower relapse rate and prolonged PFS. Therefore, R-B is a valid treatment option for FL grade 3A.

Implications For Practice: Rituximab plus bendamustine (R-B) has shown to be less toxic and more effective than rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) in follicular lymphoma grade 3A. Although both regimens can induce a complete remission in >95% of patients, relapses occur more frequently after R-CHOP than R-B, leading to a significantly longer progression-free survival in the latter. R-B is also able to overcome the impact of negative prognosticators, such as BCL2 expression. However, because of the indolent course of this disease and efficient salvage treatments, overall survival was similar in both treatment groups. Therefore, R-B is a valid treatment option in this patient setting.
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http://dx.doi.org/10.1634/theoncologist.2017-0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896707PMC
April 2018

Secondary syphilis mimicking malignancy: A case report and review of literature.

J Infect Chemother 2017 Aug 26;23(8):576-578. Epub 2017 Apr 26.

Department of Advanced Biomedical Sciences, University of Naples "Federico II", Italy.

A 56-year-old man developed disseminate lymphadenopathies, associated with hepato-splenomegaly, fever, nocturnal sweating and weight loss. Imaging studies in particular FDG-PET/CT raised the suspicion of a malignant disease. But blood flow cytometry assay for B/T cell clonality was negative and fine-needle biopsy of enlarged laterocervical lymph node showed a not specific "reactive hyperplasia". Four months later, the patient developed a non-itching rash; since a further anamnestic investigation revealed an history of high-risk sexual intercourse, the patient underwent serological tests for Treponema pallidum that were positive at high titer, after a first negative screening. Made the diagnosis of secondary syphilis, the patient responded to the treatment with benzyl penicillin with complete resolution of symptoms. This case highlights the importance of carefully screening the patients with suspected lymphoadenopathies also for lue, particularly in presence of behavioral risk factors.
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http://dx.doi.org/10.1016/j.jiac.2017.03.003DOI Listing
August 2017

A case of efficacy of bendamustine in heavily pretreated multiple myeloma, refractory to pomalidomide.

Clin Case Rep 2017 Apr 8;5(4):505-507. Epub 2017 Mar 8.

Hematology Azienda Ospedaliera Universitaria Federico II Via Pansini 5 Naples 80131 Italy.

In this report, we would like to highlight the efficacy of bendamustine in a heavily pretreated patient, also refractory to pomalidomide. It is conceivable that different therapy combinations in heavily treated Multiple myeloma (MM) have to be explored, without "a priori" exclusion of ancient drugs, even after failure of the ultimate pharmacological options.
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http://dx.doi.org/10.1002/ccr3.773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378832PMC
April 2017

Retreatment with Bendamustine-Bortezomib-Dexamethasone in a Patient with Relapsed/Refractory Multiple Myeloma.

Case Rep Hematol 2016 27;2016:6745286. Epub 2016 Oct 27.

Hematology, University Federico II, Via Pansini 5, 80131 Napoli, Italy.

The clinical management of relapsed/refractory multiple myeloma and the correct choice of the most suitable therapy in heavily pretreated and fragile patients are tough clinical issues for clinicians. In advanced phases of disease, the choice of available therapies becomes very poor, and the retreatment with previously adopted and effective therapy, although unpredictable, could be an effective option. In this report, we describe the clinical history of a patient, previously treated with 9 lines of therapy, refractory to bortezomib and IMIDs, for whom the retreatment with bendamustine resulted in a stable disease with good quality of life.
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http://dx.doi.org/10.1155/2016/6745286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102715PMC
October 2016