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Objective: We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high‐risk cytogenetic abnormalities in lenalidomide‐pretreated patients with multiple myeloma at first relapse. Methods: OPTIMISMM was a phase 3, multicenter, open‐label, randomized study (NCT01734928; N = 559). The primary endpoint was progression‐free survival (PFS). Results: Overall, 226 patients had received one prior line of therapy. PVd significantly prolonged PFS vs Vd in patients aged ≤65 years (median, 22.0 vs 13.1 months; P =.0258) and >65 years (median, 17.6 vs 9.9 months; P =.0369). Median PFS in patients with renal impairment (RI; creatinine clearance <60 mL/min) was 15.1 months with PVd vs 9.5 months with Vd (hazard ratio [HR], 0.67 [95% CI, 0.34‐1.34]). In patients without RI, median PFS was 22.0 vs 13.1 months (HR, 0.45 [95% CI, 0.27‐0.76]). In patients with high‐risk cytogenetics, median PFS was 14.7 vs 9.9 months (HR, 0.39 [95% CI, 0.13‐1.17]). PVd significantly improved overall response rate vs Vd in all subgroups. The safety profile of PVd was consistent with previous reports. Conclusions: These findings confirmed the benefits of PVd at first relapse, including in patients with poor prognostic factors. [ABSTRACT FROM AUTHOR]

We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median followup time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6&3183;3; 35·8) in patients who did not receive ASCT (P = 0&3183;001). Multivariate analyses identified age ≥60 years, platelet count ≤100 9 109/l and peripheral blood plasma cell count ≥20 9 109/l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2–3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated. [ABSTRACT FROM AUTHOR]

Rituximab is an IgG1, chimeric monoclonal antibody (mAb) containing murine light- and heavy-chain variable-region sequences and human constant-region sequences. Rituximab targets the CD20 molecule expressed on normal and malignant B-lymphocytes. At present, rituximab is the most important mAb of clinical value in patients with B-cell lymphoid malignancies. Since approval in 1997, rituximab has become widely used in chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and diffused large B-cell lymphoma (DLBCL) when combined with chemotherapy. Currently, rituximab is commonly combined with first-line chemotherapy for FL and should be offered as maintenance therapy to all appropriate patients with this disease. Randomized Phase III trials demonstrated the superiority of rituximab added to CHOP chemotherapy against CHOP chemotherapy alone in patients with DLBCL. Rituximab alone has limited activity in MCL but can be used in MCL in combination with chemotherapy, despite the benefits not being as impressive as when used against other lymphoma entities. In addition, for the less frequent B-cell lymphomas, small series show considerable activity for most of these entities. Fludarabine and rituximab combination therapies in CLL yielded promising results in several studies. Two large Phase III randomized trials demonstrated the superiority of chemoimmunotherapy with rituximab compared with chemotherapy alone in previously untreated and refractory/relapsed patients with CLL. Therefore, it can be concluded that rituximab, with only few exceptions, can generally be accepted as a standard component of anti B-cell non-Hodgkin-s lymphoma therapies. In this review, the pharmacology, mode of action, pharmacokinetics, and current place in the therapy of B-cell lymphoid malignancies of rituximab are presented. In addition, an overview of studies conducted to date and optimal use of this drug, including timing and doses, is presented [ABSTRACT FROM AUTHOR]

Isolated central nervous system involvement in Richter's syndrome (RS) is extremely rare and only 6 such cases have been described, so far. We report a 60-year-old woman with B-cell chronic lymphocytic leukemia (B-CLL) heavily pretreated with cladribine based regimens and rituximab in whom RS in the brain was first manifested as a stroke. Initial cranial computed tomography (CT) revealed a hypodense area in the right parietal lobe showing no contrast enhancement. The follow-up CT done after 2 months showed an irregular, slightly hyperdense tumor surrounded by oedema with mass effect and midline shift. However, cerebrospinal fluid (CSF) examinations revealed no pathological changes. Neurosurgical operation was performed and the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been established on the basis of histological and immunological investigation of the tumor. The pattern of immunoglobulin heavy chain (IgH) gene rearrangement in the patients' bone marrow aspirate and brain tumor was identical and suggested that both tumors originated from the same B-cell progenitors. The patient was then treated with brain irradiation (2000 cGy) and complete remission as assessed by MRI was achieved. Significant neurological improvement was observed and no clinical progression was stated 3 months after radiotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear. METHODS In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)- negative status in patients with a complete response. RESULTS A total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; PcO.OOl). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P=0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P=0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups. CONCLUSIONS Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. [ABSTRACT FROM AUTHOR]

BACKGROUND Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse. METHODS In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed. RESULTS A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group. CONCLUSIONS Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. [ABSTRACT FROM AUTHOR]

Background: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies., Methods: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status., Results: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved., Conclusions: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.)., (Copyright © 2024 Massachusetts Medical Society.)

TRU-016, under development by Trubion Pharmaceuticals Inc and Facet Biotech Corp, is an intravenously administered anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), as well as for autoimmune and inflammatory diseases. TRU-016 was created by humanizing SMIP-016, a mouse/human chimeric protein that demonstrated antitumor activity against lymphoid malignancies in preclinical studies, including in human B-cell tumor mouse xenograft models. In addition, TRU-016 demonstrated synergistic or additive activity in NHL cells in combination with rituximab, rapamycin, doxorubicin and bendamustine. In a phase I/II clinical trial in refractory or relapsed patients with CLL or small lymphocytic lymphoma, TRU-016 was well tolerated, with clinical benefit and a reduced absolute lymphocyte count observed in all cohorts dosed at > 0.1 mg/kg. TRU-016 is a promising therapeutic agent for patients with B-cell lymphoid malignancies, especially patients refractory to standard treatment.