Toxicity profile
discontinuations, nausea, Thrombocytopenia, hematological abnormalities, diarrhea, fatigue, febrile neutropenia, neutropenia, toxicity, paresthesia, vomiting, anemia, hematological abnormality, abnormal blood cell counts (grade ≥ 2), Neutropenia, peripheral neuropathy, Cancer
ADVERSE EVENT, THROMBOCYTOPENIA, NEUTROPENIA, FEBRILE NEUTROPENIA, ADVERSE EVENTS, THROMBOCYTOPENIA, PARESTHESIA, ANEMIA, NEUTROPENIA, PERIPHERAL NEUROPATHY, CANCER
The most common treatment‐related AEs found among the 36 patients treated at all dose levels were nausea (36% of patients), fatigue (28%), diarrhea (25%), and peripheral neuropathy and vomiting (19% each). Most of these AEs were grade 1/2. Grade ≥ 3 treatment‐related AEs at all dose levels comprised fatigue (Among the 24 patients treated at the RD cohort, the most frequent treatment‐related AEs were nausea (33% of patients), diarrhea (25%), fatigue (21%), and vomiting (17%). Most of these AEs were grade 1/2 (Table Treatment‐related adverse events (>10% of patients) and laboratory abnormalities at the RD cohort
Abbreviations: ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; BTZ, bortezomib; CPK, creatine phosphokinase; NCI‐CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; RD, recommended dose.The most common hematological abnormality (regardless of relationship to treatment) at all dose levels was anemia (all patients). Most cases were grade 1/2. Grade ≥ 3 anemia was found in 11 of 36 treated patients (31%). Thrombocytopenia was observed in 86% of patients reaching grade ≥ 3 in 17 patients. Neutropenia was found in 47% of patients with grade ≥ 3 in five patients. No episodes of febrile neutropenia were reported.At the RD cohort, grade ≥ 3 anemia was present in eight of 24 treated patients (33%; grade 4 in one). Thrombocytopenia was found in 83% of patients with grade ≥ 3 in 11 patients (46%; grade 4 in six). Neutropenia was found in 54% of patients, with grade 3 in four patients (Table Most patients with grade ≥ 3 hematological abnormalities at the RD already had abnormal blood cell counts (grade ≥ 2) at baseline, including six of 11 with grade 3/4 thrombocytopenia, three of four with grade 3 neutropenia, and seven of eight with grade 3/4 anemia. No treatment discontinuations, cycle delays, or dose reductions occurred at the RD due to hematological toxicity, which was managed with dose omissions.The most frequent biochemical abnormality regardless of relationship was alanine aminotransferase (ALT) increase (94%) at all dose levels, followed by aspartate aminotransferase (AST) increase (80%), creatine increase (71%), and creatine phosphokinase (CPK) increase (35%). Most transaminase increases at all dose levels were grade 1/2, and none reached grade 4. Grade 1/2 ALT increases and AST increases were reported in 26 patients each (46% of patients had grade 1 ALT increase and 57% had grade 1 AST increase). Grade 3 ALT increases were reported in seven patients (20%) and grade 3 AST increase occurred in two patients (6%).Among the 24 patients treated at the RD cohort, the most frequent biochemical abnormality regardless of relationship was ALT increase (91%), followed by AST increase (83%), creatine increase (68%), and CPK increase (36%). Most of these abnormalities at the RD cohort were grade 1/2 and none reached grade 4; grade 3 were ALT increase in six patients, and grade 3 AST increase, creatinine increase and CPK increase in one patient each (Table At the RD cohort, three treatment discontinuations occurred due to non‐hematological toxicity (grade 3 diarrhea in Cycle 2, grade 3 nausea and vomiting refractory to antiemetic therapy [DLTs] in Cycle 1, and grade 3 ALT/AST increase in Cycle 2). Six patients had dose reductions in 7 cycles. Of these, five dose reductions occurred due to toxicity, with four of them involving plitidepsin (two episodes of grade 3 ALT increase, and one episode each of grade 3 fatigue, and grade 2 CPK increase) and only one involving BTZ (grade 1 paresthesia). Two dose reductions were due to reasons unrelated to treatment. Ten patients required packed red blood cell transfusions and six were given platelet transfusions.