TY - JOUR
T1 - Efficacy of daratumumab-based therapies in patients with relapsed, refractory multiple myeloma treated outside of clinical trials
AU - Lakshman, Arjun
AU - Abeykoon, Jithma P.
AU - Kumar, Shaji K.
AU - Rajkumar, S. Vincent
AU - Dingli, David
AU - Buadi, Francis K.
AU - Gonsalves, Wilson I.
AU - Leung, Nelson
AU - Dispenzieri, Angela
AU - Kourelis, Taxiarchis V.
AU - Go, Ronald S.
AU - Lacy, Martha Q.
AU - Hobbs, Miriam A.
AU - Lin, Yi
AU - Warsame, Rahma
AU - Lust, John
AU - Fonder, Amie L.
AU - Hwa, Yi L.
AU - Hayman, Suzanne R.
AU - Russell, Stephen J.
AU - Kyle, Robert A.
AU - Gertz, Morie A.
AU - Kapoor, Prashant
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.24883
DO - 10.1002/ajh.24883
M3 - Article
C2 - 28799231
AN - SCOPUS:85029230683
SN - 0361-8609
VL - 92
SP - 1146
EP - 1155
JO - American journal of hematology
JF - American journal of hematology
IS - 11
ER -