INTRODUCTION: Two phase 3 studies demonstrated superior efficacy of intravenous daratumumab (DARA IV) plus bortezomib/melphalan/prednisone (ALCYONE) or lenalidomide/dexamethasone (Rd; MAIA) versus standard-of-care regimens for transplant-ineligible newly diagnosed multiple myeloma. In these studies, patients could switch from DARA IV to subcutaneous daratumumab (DARA SC) while receiving daratumumab monotherapy in ALCYONE (as of Cycle 11) or daratumumab plus Rd in MAIA. The phase 3 COLUMBA study demonstrated noninferiority of DARA SC to DARA IV. DARA SC reduced administration time, allowing patients to spend less time in healthcare settings, a relevant practical consideration for patient care in the COVID-19 pandemic/settings of limited healthcare resources. METHODS: DARA SC 1800 mg was administered every 4 weeks, per approved dosing schedules. We evaluated safety and patient-reported experience (ALCYONE only) among patients who switched from DARA IV to DARA SC. RESULTS: Fifty-seven patients in ALCYONE and 135 in MAIA switched to DARA SC. Three (2.2%; MAIA) patients reported injection-site reactions, all of which were mild. No infusion-related reactions occurred with DARA SC. In ALCYONE, >80% of patients preferred DARA SC over DARA IV. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 5.3% of patients in ALCYONE and 25.9% in MAIA; one (0.7%; MAIA) patient experienced a TEAE with an outcome of death. CONCLUSION: For transplant-ineligible newly diagnosed multiple myeloma, DARA SC (monotherapy/with Rd) was safe and preferred over DARA IV. ClinicalTrials.gov, NCT02195479/NCT02252172.
PURPOSE: Ibrutinib has shown activity in non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-germinal center B-cell DLBCL. PATIENTS AND METHODS: Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%). CONCLUSION: The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.
- MeSH
- Cyclophosphamide administration & dosage adverse effects MeSH
- Lymphoma, Large B-Cell, Diffuse drug therapy MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Doxorubicin administration & dosage adverse effects MeSH
- Double-Blind Method MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Young Adult MeSH
- Placebos MeSH
- Prednisone administration & dosage adverse effects MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects therapeutic use MeSH
- Pyrazoles administration & dosage adverse effects MeSH
- Pyrimidines administration & dosage adverse effects MeSH
- Rituximab administration & dosage adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Vincristine administration & dosage adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- Humans MeSH
- Lymphoma, Mantle-Cell drug therapy pathology MeSH
- International Agencies MeSH
- Survival Rate MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Pyrazoles administration & dosage MeSH
- Pyrimidines administration & dosage MeSH
- Sirolimus administration & dosage analogs & derivatives MeSH
- Salvage Therapy * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
