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

• Published in: American journal of hematology 2017-11, Vol.92 (11), p.1146-1155
• Main Authors: Lakshman, Arjun, Abeykoon, Jithma P., Kumar, Shaji K., Rajkumar, S. Vincent, Dingli, David, Buadi, Francis K., Gonsalves, Wilson I., Leung, Nelson, Dispenzieri, Angela, Kourelis, Taxiarchis V., Go, Ronald S., Lacy, Martha Q., Hobbs, Miriam A., Lin, Yi, Warsame, Rahma, Lust, John, Fonder, Amie L., Hwa, Yi L., Hayman, Suzanne R., Russell, Stephen J., Kyle, Robert A., Gertz, Morie A., Kapoor, Prashant
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Bortezomib; Chromosome Aberrations; Clinical trials; Cytogenetics; Dexamethasone; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Hematology; Humans; Immunotherapy; Male; Middle Aged; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Recurrence; Retreatment; Survival Analysis; Targeted cancer therapy; Treatment Outcome
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.24883

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 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.