Table 3.
Safety of Isa/Dara-KRd drug combination therapies in NDMM patients receiving ASCT
| Study | AEs, n (%) | Common AEs, any grade | Grade ≥ 3 AEs, n (%) | Common grade 3–4 AEs | Serious AE, n (%) |
Discontinuation due to AE, n |
Cardiac toxicity: grade ≥ 3 AEs, n (%)a |
Deaths during trial, n |
|---|---|---|---|---|---|---|---|---|
| Isa-KRd | ||||||||
| IsKia[40] |
• Hematologic: 55% Isa-KRd, 43% KRd • Non-hematologic: 90% Isa-KRd, 85% KRd |
NR |
• Hematologic: 40% Isa-KRd, 30% KRd • Non-hematologic: 41% Isa-KRd, 37% KRd |
Hematologic: • Isa-KRd: neutropenia (37%), thrombocytopenia (15%) • KRd: neutropenia (22%), thrombocytopenia (17%) Non-hematologic: • Isa-KRd: infections (16%), gastrointestinal (7%), vascular (2%), cardiac events (1%) • KRd: infections (12%), vascular (7%), gastrointestinal (5%), cardiac events (4%) |
NR |
• Isa-KRd: 6% • KRd: 5% |
NR |
• Related: Isa-KRd, 4 (COVID, 2; pneumonia, 1; pulmonary embolism, 1); KRd (septic shock), 1 • Emergent: 0 |
| GMMG-CONCEPTb[41] | 91 (94) |
• Hematologic: neutropenia (41%), thrombocytopenia (28%), leukopenia (26%), anemia (14%) • Non-hematologic: infections (61%), neuropathy (35%), infusion-related reaction (27%), gastrointestinal (20%), hypertension (14%), cardiac (11%) |
76 (78) |
• Hematologic: neutropenia (39%), thrombocytopenia (27%), leukopenia (25%), anemia (14%) • Non-hematologic: infections (28%), hypertension (10%), gastrointestinal (9%), renal (6%), neuropathy (2%), cardiac (2%), infusion-related reaction (1%) |
NR | 3 |
Cardiac events: 2 (2) |
Related/ emergent: 5 |
| Dara-KRd | ||||||||
| MASTER[43] | 123 (100) |
• Hematologic: neutropenia (42%), lymphopenia (28%), anemia (22%), thrombocytopenia (18%) • Non-hematologic: fatigue (56%), bone pain (56%), maculopapular rash (41%), infusion-related reactions (28%), hypertension (26%) |
94 (76) |
• Hematologic: neutropenia (35%), lymphopenia (23%), anemia (11%), leukopenia (10%) • Non-hematologic: fatigue (9%), bone pain (6%), maculopapular rash (4%), hypertension (11%), thromboembolic events (4%), lung infection (4%) |
22 (18) |
• 2 (for K) • 2 (for R) |
0 (1 patient grade 1–2) |
• Related: 0 • Emergent: 3 |
| LCI-HEM-MYE-KRDD-001[44–46] | 39 (100) |
• Infections (51%) • Treatment-related: diarrhea (39%), fatigue (36%), neutropenia (28%), constipation (26%), thromboembolic events (8%) |
31 (80) | Treatment-related: neutropenia (21%), hypophosphatemia (13%) | 14 (36) | NR | NR |
• Related: 1 • Emergent: 0 |
| IFM 2018–04[47] | NR |
During induction: • Hematologic: neutropenia (36%), anemia (26%), thrombocytopenia (26%) • Non-hematologic: infections (42%), fatigue (26%), diarrhea (26%), nausea (26%) During consolidation: • Hematologic: neutropenia (21%), thrombocytopenia (19%), anemia (7%) • Non-hematologic: infections (35%), diarrhea (21%), fatigue (19%) |
NR |
During induction: • Hematologic: neutropenia (32%), anemia (18%), thrombocytopenia (14%) • Non-hematologic: nausea (4%), infections (4%), psychiatric (4%), diarrhea (2%) During consolidation: • Hematologic: neutropenia (14%), thrombocytopenia (9%) • Non-hematologic: infections (5%), nausea (2%) |
NR | 4 | NR |
• Related: 2 • Emergent: 7 |
AE, adverse event; ASCT, autologous stem cell transplant; d, dexamethasone; Dara, daratumumab; Isa, isatuximab; K, carfilzomib; NDMM, newly diagnosed multiple myeloma; NR, not reported; R, lenalidomide
aDefinitions of preferred terms for cardiac toxicity listed in supplement as available
b99 patients were transplant eligible