Contributions
Abstract: PB1872
Type: Publication Only
Background
Due to the lack of prospective clinical trials, treatment guidelines for splenic marginal zone lymphoma (SMZL) are mainly based on single-center expertise. Treatment options for progressive disease include splenectomy, chemo-immunotherapy, or anti-viral therapy in HCV-positive cases. As SMZL cells strongly express CD20 molecule, rituximab has been used in patients unfit for chemotherapy or splenectomy with high response rates. Ofatumumab is a fully humanized, high-affinity anti-CD20 monoclonal antibody able to induce a more potent complement-dependent cytotoxicity if compared to rituximab. We designed this multicenter, open-label, single-arm phase 2 trial addressing activity and safety of ofatumumab monotherapy in patients with relapsed/refractory (R/R) SMZL.
Aims
The primary objective is the activity of ofatumumab in terms of complete response (CR) rate. Secondary objectives aim at evaluating the safety and tolerability and exploratory endpoints investigate biological features potentially related with response to ofatumumab.
Methods
All patients provided written informed consent. Key eligibility criteria include R/R disease after ≤2 prior line(s) of chemotherapy or immunochemotherapy (including single-agent rituximab). Patients are treated with ofatumumab (1st dose: 300 mg, 2nd-8th doses: 1000 mg) up to 8 weekly doses. Response assessment is scheduled 3 months after the last dose. Sample size was defined assuming a P0 of 45% CR, and a P1 of 65% CR. Per Simon optimal Two-Stage design (type I error = 0.05, power = 80%), 43 patients should be recruited. A safety analysis was planned after the enrollment of the first 10 patients. With an expected rate of adverse events (AEs) of 13%, if less than 3 AEs leading to withdrawal from treatment are reported, the accrual will continue to the planned 15 patients (interim analysis). Here we present safety analysis results.
Results
Ten patients (6 males, 4 females; median age: 69.5 years, 9 ≥ 65 years, 1 < 65 years) were analyzed for safety. Eight patients were previously treated with rituximab. 26 adverse events (AEs) occurred in 7 patients, with only 5 grade 3-4 AEs. Ten AEs were drug-related, 30% were of grade 3 (Table 1). Three SAEs occurred: hypersensitivity, n=2, both related, and dyspnea, n=1, unrelated to study drug. No AEs leading to treatment withdrawal was reported and no patients died on study. Hematological and biochemical abnormalities included: neutropenia (any grade 6 cases, grade 3-4: 4), thrombocytopenia (grade 1-2: 3 cases), lymphopenia (grade 1-2: 2 cases), leukopenia (grade 1-2: 5 cases), 1 case of GGT increase (grade 3, at baseline grade 2), 6 cases of ALP increase (all grade 1-2), 1 case each of AST, ALT and bilirubin increase (all grade 1). Preliminary response assessment in these 10 patients documented 5 CR, 4 Partial Responses (PR) and one patient with progressive disease (PD) at the end of treatment. Table 1: List of AEs.
Drug-related AEs | N of events (any grade/grade 3-4) | Non-drug related AEs | N of events (any grade/grade 3-4) |
Neutropenia | 2 (2) | Neutropenia | 1 (1) |
Flushing | 2 (0) | Anemia | 1 (1) |
Hypersensitivity | 3 (1) | Neoplasm of nasopharynx | 1 (1) |
Throat irritation | 1 (0) | Fatigue | 2 (0) |
Post herpetic neuralgia | 1 (0) | Dyspnea, orthopnea | 2 (0) |
Hypertension | 1 (0) | Pleural effusion, pulmonary failure | 3 (0) |
Bone pain | 2 (0) | ||
Constipation | 1 (0) | ||
Oral herpes | 1 (0) | ||
Pelvic pain | 1 (0) | ||
Atrial fibrillation | 1 (0) |
Conclusion
Ofatumumab is safe and generally well-tolerated even in elderly patients with R/R SMZL. No cases of unexpected adverse drug reactions were documented. In a series of patients largely pre-treated with rituximab, ofatumumab resulted in a 90% overall response rate, 50% being CR. Complete results of the interim analysis will be presented at meeting.
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): Splenic marginal zone lymphoma, Relapse, Monoclonal antibody
Abstract: PB1872
Type: Publication Only
Background
Due to the lack of prospective clinical trials, treatment guidelines for splenic marginal zone lymphoma (SMZL) are mainly based on single-center expertise. Treatment options for progressive disease include splenectomy, chemo-immunotherapy, or anti-viral therapy in HCV-positive cases. As SMZL cells strongly express CD20 molecule, rituximab has been used in patients unfit for chemotherapy or splenectomy with high response rates. Ofatumumab is a fully humanized, high-affinity anti-CD20 monoclonal antibody able to induce a more potent complement-dependent cytotoxicity if compared to rituximab. We designed this multicenter, open-label, single-arm phase 2 trial addressing activity and safety of ofatumumab monotherapy in patients with relapsed/refractory (R/R) SMZL.
Aims
The primary objective is the activity of ofatumumab in terms of complete response (CR) rate. Secondary objectives aim at evaluating the safety and tolerability and exploratory endpoints investigate biological features potentially related with response to ofatumumab.
Methods
All patients provided written informed consent. Key eligibility criteria include R/R disease after ≤2 prior line(s) of chemotherapy or immunochemotherapy (including single-agent rituximab). Patients are treated with ofatumumab (1st dose: 300 mg, 2nd-8th doses: 1000 mg) up to 8 weekly doses. Response assessment is scheduled 3 months after the last dose. Sample size was defined assuming a P0 of 45% CR, and a P1 of 65% CR. Per Simon optimal Two-Stage design (type I error = 0.05, power = 80%), 43 patients should be recruited. A safety analysis was planned after the enrollment of the first 10 patients. With an expected rate of adverse events (AEs) of 13%, if less than 3 AEs leading to withdrawal from treatment are reported, the accrual will continue to the planned 15 patients (interim analysis). Here we present safety analysis results.
Results
Ten patients (6 males, 4 females; median age: 69.5 years, 9 ≥ 65 years, 1 < 65 years) were analyzed for safety. Eight patients were previously treated with rituximab. 26 adverse events (AEs) occurred in 7 patients, with only 5 grade 3-4 AEs. Ten AEs were drug-related, 30% were of grade 3 (Table 1). Three SAEs occurred: hypersensitivity, n=2, both related, and dyspnea, n=1, unrelated to study drug. No AEs leading to treatment withdrawal was reported and no patients died on study. Hematological and biochemical abnormalities included: neutropenia (any grade 6 cases, grade 3-4: 4), thrombocytopenia (grade 1-2: 3 cases), lymphopenia (grade 1-2: 2 cases), leukopenia (grade 1-2: 5 cases), 1 case of GGT increase (grade 3, at baseline grade 2), 6 cases of ALP increase (all grade 1-2), 1 case each of AST, ALT and bilirubin increase (all grade 1). Preliminary response assessment in these 10 patients documented 5 CR, 4 Partial Responses (PR) and one patient with progressive disease (PD) at the end of treatment. Table 1: List of AEs.
Drug-related AEs | N of events (any grade/grade 3-4) | Non-drug related AEs | N of events (any grade/grade 3-4) |
Neutropenia | 2 (2) | Neutropenia | 1 (1) |
Flushing | 2 (0) | Anemia | 1 (1) |
Hypersensitivity | 3 (1) | Neoplasm of nasopharynx | 1 (1) |
Throat irritation | 1 (0) | Fatigue | 2 (0) |
Post herpetic neuralgia | 1 (0) | Dyspnea, orthopnea | 2 (0) |
Hypertension | 1 (0) | Pleural effusion, pulmonary failure | 3 (0) |
Bone pain | 2 (0) | ||
Constipation | 1 (0) | ||
Oral herpes | 1 (0) | ||
Pelvic pain | 1 (0) | ||
Atrial fibrillation | 1 (0) |
Conclusion
Ofatumumab is safe and generally well-tolerated even in elderly patients with R/R SMZL. No cases of unexpected adverse drug reactions were documented. In a series of patients largely pre-treated with rituximab, ofatumumab resulted in a 90% overall response rate, 50% being CR. Complete results of the interim analysis will be presented at meeting.
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): Splenic marginal zone lymphoma, Relapse, Monoclonal antibody