Gr 3 to 4 AEs associated with combination therapy with duv/romi in multicenter R/R cohort
| AE . | n (%) (n = 36) . | Time to event∗ (mo), median (IQR) . | Dose delay† due to AE, n (%) . |
|---|---|---|---|
| Hematologic | 26 (72) | 5/36 (14) | |
| Neutropenia | 15 (42) | 0.5 (0.2-1.4) | 2/36 (6) |
| Gr 3 | 5 (14) | 1RD (3) | |
| Gr 4 | 10 (28) | 1RD, 1D (6) | |
| Febrile neutropenia | 4 (11) | 2.2 (2.1-2.7) | 0 |
| Gr 3 | 3 (8) | 2RD‡ (6) | |
| Gr 4 | 1 (3) | ||
| Anemia, gr 3 | 6 (17) | 1.9 (0.2-4.2) | 0 |
| Thrombocytopenia | 10 (28) | 1.6 (0.4-1.9) | 4/36 (11) |
| Gr 3 | 2 (6) | 1RD (3) | |
| Gr 4 | 8 (22) | 1RD, 2R (8) | |
| Lymphopenia | 15 (42) | 2.2 (0.8-3.0) | 0 |
| Gr 3 | 10 (28) | ||
| Gr 4 | 5 (14) | ||
| Leukocytosis | 4 (11) | 0.2 (0-1.2) | 0 |
| Gr 3 | 3 (8) | — | |
| Gr 4 | 1 (3) | ||
| Gastrointestinal | 9 (25) | 5/36 (14) | |
| Transaminitis (ALT elevation) | 6 (17) | 2.0 (1.7-2.6) | 5/36 (14) |
| Gr 3 | 5 (14) | 2RD,§ 2D (6) | |
| Gr 4 | 1 (3) | 1RD,D (3) | |
| Transaminitis (AST elevation) | 6 (17) | 1.1 (1.0-1.7) | 3/36 (8) |
| Gr 3 | 1RD,D, 2D (8) | ||
| Enterocolitis | 2 (6) | 2.8 (2.5-3.2) | 1/36 (3) |
| Gr 3 | 1D‖ (3) | ||
| Noninfectious diarrhea | 3.39 | 1/36 (3) | |
| Gr 4 | 1 (3) | 1D‖ (3) | |
| Alkaline phosphatase elevation | 0 | — | 0 |
| Infectious | 9/29 (38) | 3/36 (8) | |
| Cytomegalovirus viremia¶ | 5/29 (17) | 1.2 (1.1-1.4) | 0 |
| TB reactivation | 1 (3) | — | 1R (3) |
| COVID-19 infection | 2 (6) | — | 2RD (6) |
| Pseudomonas bacteremia | 1 (3) | — | 0 |
| Klebsiella bacteremia | 1 (3) | — | 0 |
| Other gr 3 and 4 AEs | 10 (28) | 3/36 (8) | |
| Rash | 5 (14) | 9.5 (1.2-9.9) | 1R (3) |
| Fatigue (gr 3) | 6 (17) | 2.1 (1.5-2.4) | 1D, 1RD (6) |
| Anorexia | 0 | — | 0 |
| AE . | n (%) (n = 36) . | Time to event∗ (mo), median (IQR) . | Dose delay† due to AE, n (%) . |
|---|---|---|---|
| Hematologic | 26 (72) | 5/36 (14) | |
| Neutropenia | 15 (42) | 0.5 (0.2-1.4) | 2/36 (6) |
| Gr 3 | 5 (14) | 1RD (3) | |
| Gr 4 | 10 (28) | 1RD, 1D (6) | |
| Febrile neutropenia | 4 (11) | 2.2 (2.1-2.7) | 0 |
| Gr 3 | 3 (8) | 2RD‡ (6) | |
| Gr 4 | 1 (3) | ||
| Anemia, gr 3 | 6 (17) | 1.9 (0.2-4.2) | 0 |
| Thrombocytopenia | 10 (28) | 1.6 (0.4-1.9) | 4/36 (11) |
| Gr 3 | 2 (6) | 1RD (3) | |
| Gr 4 | 8 (22) | 1RD, 2R (8) | |
| Lymphopenia | 15 (42) | 2.2 (0.8-3.0) | 0 |
| Gr 3 | 10 (28) | ||
| Gr 4 | 5 (14) | ||
| Leukocytosis | 4 (11) | 0.2 (0-1.2) | 0 |
| Gr 3 | 3 (8) | — | |
| Gr 4 | 1 (3) | ||
| Gastrointestinal | 9 (25) | 5/36 (14) | |
| Transaminitis (ALT elevation) | 6 (17) | 2.0 (1.7-2.6) | 5/36 (14) |
| Gr 3 | 5 (14) | 2RD,§ 2D (6) | |
| Gr 4 | 1 (3) | 1RD,D (3) | |
| Transaminitis (AST elevation) | 6 (17) | 1.1 (1.0-1.7) | 3/36 (8) |
| Gr 3 | 1RD,D, 2D (8) | ||
| Enterocolitis | 2 (6) | 2.8 (2.5-3.2) | 1/36 (3) |
| Gr 3 | 1D‖ (3) | ||
| Noninfectious diarrhea | 3.39 | 1/36 (3) | |
| Gr 4 | 1 (3) | 1D‖ (3) | |
| Alkaline phosphatase elevation | 0 | — | 0 |
| Infectious | 9/29 (38) | 3/36 (8) | |
| Cytomegalovirus viremia¶ | 5/29 (17) | 1.2 (1.1-1.4) | 0 |
| TB reactivation | 1 (3) | — | 1R (3) |
| COVID-19 infection | 2 (6) | — | 2RD (6) |
| Pseudomonas bacteremia | 1 (3) | — | 0 |
| Klebsiella bacteremia | 1 (3) | — | 0 |
| Other gr 3 and 4 AEs | 10 (28) | 3/36 (8) | |
| Rash | 5 (14) | 9.5 (1.2-9.9) | 1R (3) |
| Fatigue (gr 3) | 6 (17) | 2.1 (1.5-2.4) | 1D, 1RD (6) |
| Anorexia | 0 | — | 0 |
Superscript “RD” represents romi and duv delay, whereas “D” and “R” indicate duv and romi delay, respectively.
Time to event was measured from treatment start date to date of AE and only reported in patients who had an AE.
Dose delays were defined as a held dose due to an AE resulting in a deviation from the treatment plan for either duv, romi, or both in any treatment cycle. If a patient experienced dose delays in multiple treatment cycles due to a single AE, they were counted as 1 delay. Dose delays often but not always coincided with dose modifications.
Febrile neutropenia gr 3 and neutropenia gr 4 with secondary Pseudomonas (n = 1) and Klebsiella bacteremia (n = 1) led to discontinuation of duv/romi therapy in 2 patients.
Transaminitis with ALT elevation led to discontinuation of duv/romi therapy (n = 1).
Duv-associated gr 3 enterocolitis and gr 4 noninfectious diarrhea led to duv/romi treatment discontinuation (n = 1).
Nine patients had no cytomegalovirus polymerase chain reaction values available during duv/romi regimen, and therefore, 29 patients were evaluable.