Brentuximab vedotin induced objective responses in the majority of patients and CRs in more than half of patients with recurrent systemic ALCL. Targeted therapy with this CD30-directed antibody-drug conjugate may be an effective treatment for relapsed or refractory systemic ALCL and warrants further studies in front-line therapy.

Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel, highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with either ibrutinib or zanubrutinib. The primary endpoint was the proportion of patients achieving a complete or very good partial response (CR or VGPR) by independent review. Key secondary endpoints included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib and 19 (19%) ibrutinib patients achieved a VGPR, a non-statistically significant difference (P = .09). MRRs were 77% and 78% , respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression-free at 18 months. Incidence of atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were all lower among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events/100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.

• Pomalidomide plus lowdose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma.• Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ‡2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM1LoDEX (n 5 113) or POM (n 5 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio 5 0.68, P 5 .003), overall response rates (ORRs) were 33% and 18% (P 5 .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM1LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM1 LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM1LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833. (Blood. 2014;123(12):1826-1832 Introduction Virtually all patients with multiple myeloma (MM) eventually relapse. Relapsed disease is characterized by increasingly shorter periods of remission following each salvage therapy.1 Survival among MM patients in whom novel agents (including bortezomib [BORT], lenalidomide [LEN], and/or thalidomide) have failed is especially poor.2 There is a clear unmet need for new treatments, particularly for patients who are relapsed and refractory to novel agents.Pomalidomide (POM) is a distinct immunomodulatory drug with potent antimyeloma activity.3-5 POM plus dexamethasone (DEX) has synergistic antiproliferative effects in LEN-resistant myeloma cells. 6 The activity of POM in cells resistant or refractory to LEN may be due to important differences in both the potency of the drugs and their respective mechanisms of action. 3,[7][8][9][10][11] POM has demonstrated efficacy in patients with relapsed/ refractory MM (RRMM) who had received multiple prior therapies, either when given alone [12][13][14] or with low-dose DEX (LoDEX). 14-17Here, we report the results of a multicenter, randomized, open-label, phase 2 trial. The phase 1 part of the study established the maximum tolerated dose of POM (4 mg/day on days 1-21 of a 28-day cycle). 18The phase 2 part evaluated the efficacy and s...