Encouraging phase II safety and efficacy data of inotuzumab ozogamicin (InO) in patients

This article was written by Dr Andre Goy from the John Theurer Cancer Center, HUMC, Hackensack, NJ along with his colleagues and was published in the British Journal of Haematology in August 2016. The article evaluates the safety and efficacy of inotuzumab ozogamicin (InO, CMC-544) as a single agent in patients with indolent B-cell non-Hodgkin's lymphoma, who were refractory to rituximab alone, rituximab in combination with chemotherapy or anti-CD20 radioimmunotherapy (RIT). (www.clinicaltrials.gov, NCT00868608).

Patients and treatment regimen

• Patients enrolled either had follicular lymphoma (FL) [n=72 (89%)], marginal zone lymphoma (MZL) [n=4 (5%)] or small lymphocytic lymphoma (SLL) [n=5 (6%)]. 
• At screening, 83% of patients were in stage III/IV of the disease
• InO was administered at a dose of 1.8 mg/m² IV on a 28-day cycle for a minimum of 4 cycles 

Endpoints

• Primary: overall response [OR, CR or partial response (PR)]. 
• Secondary: CR, progression-free survival (PFS), duration of response (DoR) and overall survival (OS).

The key findings of the article were as follows:

Efficacy analysis

• ORR=67%  and 25 out of 81 patients (31%) achieved a CR.
• Patients with low-, intermediate- and high-risk FLIPI scores had an ORR of 75% (48–93%), 70% (46–88%) and 69% (52– 84%) respectively.
• ORR (95% CI) was 52% (31–72%), 78% (56–93%) and 70% (51–84%); CR was 24%, 22% and 42% in patients with 2, 3 and ≥4 prior therapies, respectively.
• PFS was 12.7 months (8.9–26.9) and the median OS (95% CI) was NR (26.6–NR).
• For Patients with FL, MZL and SLL: PFS was 14.7 (11.0–NR), 8.8 (3.6–17.0) and 2.4 (1.7–5.8); OS was not reached (NR), 11.4 (3.6–NR) and 14.6 (2.4–16.6) months.

Safety analysis:

• Grade ≥3 adverse events such as neutropenia (36%), lymphopenia (14%), thrombocytopenia (56%), nausea (5%), fatigue (2%), leucopenia (12%) and increased aspartate aminotransferase (AST) (2%) were reported in patients (n=81)
• Eighty six percent of patients (n=70) experienced grade 3/4 laboratory abnormalities: low platelets (59%), low white blood cell count (15%), high gamma glutamyl transferase (GGT; 12%), low ANC (33%) and lymphopenia (41%) while receiving InO.
• There were on-study deaths (n=22, 27%) and the most common reason for death in patients (n=16) was due to progressive disease.

Conclusions:

In this study, InO demonstrated anti-tumor activity, which was observed across all the patient subgroups. MZL or SLL patients responded less to InO when compared to FL patients and therefore, the small sample size of MZL and SLL patients (4 and 5, respectively), makes the results difficult to analyse. Future studies are need to establish if different dosing regimens would reduce toxicity, increase efficacy and longer treatment duration in iNHL patients.

Abstract

A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy

This phase 2 study evaluated the efficacy and safety of inotuzumab ozogamicin (InO) in patients with indolent B-cell non-Hodgkin lymphoma (NHL) refractory to rituximab alone, rituximab plus chemotherapy or antiCD20 radioimmunotherapy. Patients received InO 1.8 mg/m² intravenously on a 28-d cycle for a planned 4–8 cycles. The initial InO dose and schedule could be adjusted for tolerability and patients were allowed to receive 2 additional cycles (up to 8 total) after achieving a complete response (CR). The primary endpoint was overall response. Eighty-one patients were enrolled, among whom 48 (59%) received ≥3 InO cycles and 13 (16%) completed the treatment phase. The overall response rate was 67% (CR, 31%). Median (95% confidence interval) progression-free survival was 12.7 (8.9–26.9) months; median overall survival was not reached. Haematological adverse events (AEs) were common, particularly thrombocytopenia (74%) and neutropenia (56%). These were also the most common AEs leading to treatment discontinuation (37% and 11%, respectively); 58% of patients reported AEs leading to treatment discontinuation. InO demonstrated robust activity in these heavily pretreated patients, although treatment duration was limited by haematological toxicities. Additional studies may determine dosing regimens that allow for reduced toxicity.