Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study.

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37-82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3-12). The median number of BM cycles administered was three (range, 1-22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population.

Adverse Events Induced by PD-1/PD-L1 Inhibitors: A Real-World Single-Centre Experience with a Management-Based Approach.

AIM: To assess the efficacy and tolerance of programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) inhibitors and the impact of a standardised management-based protocol in a real-world setting. PATIENTS AND METHODS: Data from patients who had received anti-PD-(L)1 were collected from our pharmacy database. Clinical response and toxicity were assessed using RECIST criteria and CTCAE version 5.0, respectively. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method. Potential prognostic factors were identified using Cox's model. RESULTS: A total of 196 patients and 201 lines of treatment were included (median age: 66 (range: 38-89) years). Types of cancer included non-small cell lung cancer (73%), transitional cell carcinoma (10%), renal cell carcinoma (6%), small cell lung cancer (5%), head and neck squamous cell carcinoma (4%) and classical Hodgkin's lymphoma (1%). Twenty-five (12%) patients had pre-existing autoimmune conditions. Our standardised management-based protocol included 129 (64%) patients. Objective response rate was 29%, median OS was 10 months (IQR: 7-15) and median PFS was 5 months (IQR: 1-22). Patients with an abnormal baseline complete blood count had a worse OS (HR=2.48 [95% CI: 1.24-4.96]; p=0.0103). Thirty-three (16%) patients experienced severe (grade 3 or 4) immune-related adverse event (irAE). There were three (1%) irAE-related deaths. AEs resolved faster when patients were assessed by an internist before anti-PD-(L)1 initiation (p=0.0205). CONCLUSION: PD-1 and PD-L1 inhibitors are effective and safe in a real-world setting. Implementation of a standardised management-based protocol with internal medicine specialists is an effective way to optimise irAE management.

HHV8 and Kaposi's sarcoma: should we really give up protease inhibitors in all HIV-infected patients?

: We describe the first case of a patient presenting Kaposi's sarcoma with human herpes virus 8 (HHV8) viremia after switching from a protease inhibitor to an integrase inhibitor-based combination antiretroviral therapy, followed by a rapid remission when resuming protease inhibitor. We suggest that the recent recommendations to switch all HIV patients to protease inhibitor-free regimens should be carefully re-evaluated especially in MSM HIV patients which are at higher risks of HHV8 infections and associated malignancies.

Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome.

PURPOSE: Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. PATIENTS AND METHODS: Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). RESULTS: Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). CONCLUSION: In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.

E6a2 BCR-ABL fusion with BCR exon 5-deleted transcript in a Philadelphia positive CML responsive to Imatinib.

Chronic myeloid leukemia (CML) is characterized in 90% of patients by the presence of the reciprocal translocation t(9;22)(q34;q11) leading to the fusion of the BCR and ABL genes. Most patients with Philadelphia chromosome positive CML express either the e13a2 (b2a2) or e14a2 (b3a2) MBCR-ABL mRNA. Some variant cases have been reported expressing the fusion e1a2 (mBCR-ABL) or e19a2 (microBCR-ABL). Very rare atypical transcripts such as e13a3, e14a3 or e6a2 have been described. We report here a sixth case of a Ph positive patient with an e6a2 BCR-ABL fusion transcript and describe for the first time a chimeric molecule alternatively spliced for exon 5 of the BCR gene.

One versus two high-dose cytarabine-based consolidation before autologous stem cell transplantation for young acute myeloblastic leukaemia patients in first complete remission.

We report on a randomized trial aimed to determine the impact of a second consolidative high-dose cytarabine-based chemotherapy (HiDAC) in patients with acute myeloid leukaemia prior to an autologous stem cell transplantation (ASCT). Patients aged 18-60 years, in complete remission (CR) received a first consolidation with daunorubicin and cytarabine at reduced dose. Patients not allocated to allogeneic transplantation received one course of HiDAC and then were randomized to receive an ASCT immediately (HiDAC 1 group) or after one more course of HiDAC (HiDAC 2 group). Out of the 437 initial patients, 351 achieved CR (80%), of those 277 (79%) were eligible for first HiDAC, and 128 (36%) were randomized (HiDAC 1:65, HiDAC 2:63). Overall survival, leukaemia-free survival and cumulative incidence of relapse and non-relapse deaths were 41% and 53% (P = 0.14), 39% and 48% (P = 0.12), 57% and 47% (P = 0.11), 8% and 8% (P = 0.95) for HiDAC 1 and HiDAC 2 groups, respectively. Further studies are warranted with a larger number of patients to test the place of a second course of HiDAC in this setting.