Efficacy of daratumumab-based therapies in patients with relapsed, refractory multiple myeloma treated outside of clinical trials.

Abstract

Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4.3 years (range, 0.4-13.0). Seventeen (13%) patients were refractory to single agent daratumumab. Fifty-two (41%), 34 (27%), 23 (18%), and 17 (14%) received DPd, DRd, DVd and "other" DCTs, respectively. Overall response rate was 47%. Median follow-up was 5.5 months (95% CI, 4.2-6.1). Median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-7.8). Median overall survival was not reached (NR) with any regimen. Median PFS (months) was worst for penta-refractory MM (n = 8) vs quadruple refractory MM (n = 18) and others (n = 100) (2.2 [95% CI, 1-2.4] vs 3.1 [95% CI, 2.1-NR] vs 5.9 [95% CI, 5.0-NR]; P < .001); those who were refractory to ≥1 agents used in the DCT vs others (4.9 [95% CI, 3.1-6.0] vs 8.2 [95% CI, 4.6-NR]; P = .02); and those who received >2 prior therapies vs others (5.0 months [95% CI, 3.7-5.9] vs NR [95% CI, NR-NR]; P = .002). Non-hematologic toxicities included infections (38%), fatigue (32%), and infusion reactions (18%). Grade 3 or higher hematological toxicities were seen in 41% of patients. DCTs are effective in RRMM. ORR and PFS in heavily pretreated patients are lower than those reported in clinical trials.

• Authors: Arjun Lakshman, Jithma P Abeykoon, Shaji K Kumar, S Vincent Rajkumar, David Dingli, Francis K Buadi, Wilson I Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V Kourelis, Ronald S Go, Martha Q Lacy, Miriam A Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L Fonder, Yi L Hwa, Suzanne R Hayman, Stephen J Russell, Robert A Kyle, Morie A Gertz, Prashant Kapoor
• Journal: American journal of hematology (Am J Hematol) Vol. 92 Issue 11 Pg. 1146-1155 (Nov 2017) ISSN: 1096-8652 [Electronic] United States
• PMID: 28799231 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antibodies, Monoclonal
• Biomarkers
• daratumumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers
• Chromosome Aberrations
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Multiple Myeloma (diagnosis, drug therapy, mortality)
• Recurrence
• Retreatment
• Survival Analysis
• Treatment Outcome