Peripheral Neuropathy in the Phase 3 ASPEN Study of Bruton Tyrosine Kinase Inhibitors for Waldenström Macroglobulinemia.

Peripheral neuropathy (PN) is a significant cause of morbidity associated with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. This ad hoc analysis examined treatment outcomes with zanubrutinib or ibrutinib on PN symptoms associated with WM in patients enrolled in ASPEN.

Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed/refractory multiple myeloma.

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity.

Plain Language Summary of the iNNOVATE study: ibrutinib plus rituximab is well-tolerated and effective in people with Waldenström's macroglobulinemia.

What Is This Summary About?: This article provides a short summary of 5-year results from the iNNOVATE trial. The original paper was published in the in October 2021. People with Waldenström's macroglobulinemia (WM) were randomly divided into two groups of 75 people each.

Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results.

ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen.

Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study.

Purpose: The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE.

Methods: Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen.

Single-Agent Ibrutinib for Rituximab-Refractory Waldenström Macroglobulinemia: Final Analysis of the Substudy of the Phase III Innovate Trial.

Purpose: The first report from the open-label substudy of the phase III iNNOVATE study (PCYC-1127; NCT02165397) demonstrated that single-agent ibrutinib was efficacious and well tolerated in patients with heavily pretreated, rituximab-refractory Waldenström macroglobulinemia. Results from the final analysis are now reported.

Patients And Methods: Ibrutinib 420 mg was administered once daily to patients ( = 31) who failed to achieve at least a minor response (MR) or who relapsed <12 months after their last rituximab-containing therapy.

A phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed or relapsed/refractory multiple myeloma: Final analysis of second dose-expansion cohort.

The maximum tolerated dose of the panobinostat and carfilzomib combination in patients with relapsed/refractory multiple myeloma (RRMM) was not reached in our previous dose-escalation study. We report additional dose levels in the phase I/II, single-arm, multicenter, standard 3 + 3 dose-escalation expansion-cohort study (NCT01496118). Patients with RRMM were treated with panobinostat 30 mg, carfilzomib 20/56 mg/m (N = 3), or panobinostat 20 mg, carfilzomib 20/56 mg/m (N = 33).

Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma.

Patients with multiple myeloma (MM) inevitably relapse on initial treatment regimens, and novel combination therapies are needed. Ibrutinib is a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, an enzyme implicated in growth and survival of MM cells. Preclinical data suggest supra-additivity or synergy between ibrutinib and proteasome inhibitors (PIs) against MM.

Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma.

Purpose: Observation is the current standard of care for smoldering multiple myeloma. We hypothesized that early intervention with lenalidomide could delay progression to symptomatic multiple myeloma.

Methods: We conducted a randomized trial that assessed the efficacy of single-agent lenalidomide compared with observation in patients with intermediate- or high-risk smoldering multiple myeloma.

Combination trial of duvelisib (IPI-145) with rituximab or bendamustine/rituximab in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia.

Duvelisib, a potent δ- and γ-PI3K inhibitor, is a potential therapeutic for hematologic malignancies. Rituximab and bendamustine have demonstrated activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Combining duvelisib with either rituximab alone or rituximab and bendamustine may improve response rates and remission durability.

Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia.

Background: Single-agent ibrutinib has shown substantial activity in patients with relapsed Waldenström's macroglobulinemia, a rare form of B-cell lymphoma. We evaluated the effect of adding ibrutinib to rituximab in patients with this disease, both in those who had not received previous treatment and in those with disease recurrence.

Methods: We randomly assigned 150 symptomatic patients to receive ibrutinib plus rituximab or placebo plus rituximab.

Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma.

This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed.

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial.

Background: In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease.

Brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive haematologic malignancies and hepatic or renal impairment.

Aims: Brentuximab vedotin, an antibody-drug conjugate (ADC), selectively delivers the microtubule-disrupting agent monomethyl auristatin E (MMAE) into CD30-expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30-positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment.

Active idiotypic vaccination versus control immunotherapy for follicular lymphoma.

Purpose: Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF.

Patients And Methods: Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone.

Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy.

Older adults constitute a significant proportion of the cancer population, but are underrepresented in clinical trials. We conducted a retrospective analysis of the safety and efficacy of brentuximab vedotin in adults ≥ 60 years with relapsed CD30-positive lymphomas. Baseline characteristics and safety data were compared for older (median age 66) and younger patients (< 60 years, median age 32).

CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies.

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells. This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE. Two 21-day cycles of brentuximab vedotin (1.

An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma.

Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m(2) for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m(2) for cycle 1 and then 27 mg/m(2) for all subsequent cycles.