Phase II Trial of Abbreviated CHOP-Rituximab Followed by 90Y Ibritumomab Tiuxetan (Zevalin) and Rituximab in Patients with Previously-Untreated Follicular Non-Hodgkin Lymphoma (NHL).
Authors: DeMonaco Nicholas A. , Wu Michael , Osborn Jennifer , Evans Terry , Foon Kenneth A. , Swerdlow Steven H. , Kant Jeffrey , Joyce Judith , Land Stephanie R. , Jacobs Samuel A. 
Published: April 2020

Background: CHOP-rituximab (CHOP-R) and radioimmunotherapy (RIT) have demonstrated efficacy in the treatment of follicular NHL. The combination of these agents as initial therapy is a novel strategy which has been previously reported with promising results (Hainsworth et al. Proc ASCO.2005;23,Abstract 6577). We report the safety and efficacy of this approach in a single-institution, non-randomized, phase II trial with abbreviated CHOP-R followed by Zevalin and rituximab. The rationale for following Zevalin with additional rituximab includes the potential beneficial effect of extended therapy and the possible vaccinal effect (Cartron et al. Blood.2004;104,2635).

Methods: Eligible patients have CD20 positive follicular NHL, Grade 1–3, Stage II-IV, no prior treatment with monoclonal antibody or chemotherapy, and symptomatic disease. CHOP-R is first given in standard doses every 21 days for 3 cycles. Four weeks after the last dose of CHOP-R, patients receive the Zevalin regimen. One week after the therapeutic Zevalin dose, patients receive rituximab 375 mg/m2 IV weekly for 4 doses. Bone marrow examination and fusion PET-CT scans were performed at baseline, after CHOP-R, and 12 weeks after RIT. For this study, a complete remission required both functional imaging with positron emission tomography (PET) scanning showing no areas of FDG-avidity and the International Working Group criteria including CT scanning.

Results: At the planned interim analysis after accrual of 19 patients, 8 patients have completed therapy and follow-up studies and are fully evaluable. For these 8 patients with follicular NHL, two were Grade 1, three were Grade 2, and three were Grade 3. Half had Stage III disease and half had Stage IV. The median age was 59 (range 45–77). Two patients had a FLIPI score of 1 (low risk), four patients had a score of 2 (intermediate risk), and two patients had a score of 3 (poor risk). The overall response rate after 3 cycles of CHOP-R was 75% with a CR in 2 of these 8 patients (25%). After treatment with Zevalin and rituximab, 7 of 8 (87.5%) achieved a CR (CR/CRu with negative PET scan). During treatment with CHOP-R, 2 patients had Grade 3/4 neutropenia, and 1 patient had Grade 4 hyperglycemia. After treatment with Zevalin, 4 patients developed Grade 3/4 thrombocytopenia, and 4 patients developed Grade 3/4 neutropenia. During the Zevalin phase, there were no episodes of neutropenic fever.

Conclusions: Three cycles of CHOP-R followed by Zevalin and rituximab is effective in inducing a CR (CR/CRu) in previously-untreated patients with follicular NHL, decreases exposure to anthracyclines, and is a promising regimen for initial therapy. In this trial, the CR rate of 25% after CHOP-R increased to 87.5% after treatment with Zevalin and rituximab. Functional imaging with fusion PET-CT may be a more sensitive technique than CT scanning in determining residual tumor. This trial continues to accrue patients, and additional time is needed to determine the duration of response and time to next therapy.