Frontline VR-CAP Is Effective and Well Tolerated in MZL

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Bortezomib (Velcade), rituximab (Rituxan), cyclophosphamide, doxorubicin hydrochloride, prednisone, and cytarabine hydrochloride (VR-CAP) generated robust responses with a tolerable safety profile when delivered as first-line therapy in patients with marginal zone lymphoma (MZL), according to findings from a phase 2 trial (NCT04433156) presented at the 2023 ESMO Congress.¹

The 2-year progression-free survival (PFS) rate was 82.2%, and the overall response rate (ORR) was 82.0%.¹

As of February 2023, 15 patients completed the cumulative 6 course treatment, 6 patients completed 4 courses of the total 6, and 2 discontinued the treatment of their own accord. In 22 patients, a curative effect could be evaluated. Among the 22 patients, 16 (72.7%) experienced either a complete response (CR) or unconfirmed complete response (CRu) and 5 patients (22.7%) experienced a partial response (PR).

“The primary end point was the 2-year PFS [rate], and the secondary end point was ORR, including CR and PR; total survival, and security,” Junfeng Chu, MD, and coauthors, wrote in a poster of the data. “VR-CAP [as] first-line treatment of lymphoma in the marginal region has a good effect…and [is] well tolerated.”¹

The single-arm, multicenter study evaluated 23 patients with a median age of 55 years (range, 25-74). Eighteen patients (78%) were under 60 years of age, and 5 patients (22%) were 60 years or older. The male-to-female ratio was 14 to 9. Of the 23 patients, most (65%) had stage III or IV B-cell non-Hodgkin MZL (65%), and 35% of patients had stage I or II disease.

Eleven (47.8%) patients had a Follicular Lymphoma International Prognostic Index (FLIPI) of 0 to 1, 10 patients (43.5%) had a FLIPI score of 2 to 3, and 2 patients (8.7%) had a FLIPI score of 4. Turning to FLIPI-2 scores, 8 patients (34.8%) had a score of 0 to 1, 13 patients (56.5%) had a score of 2 to 2, and 2 patients (8.7%) had a score of 2.

Among the 23 patients, 2 patients (8.7%) experienced B symptoms while undergoing treatment compared with 21 patients (91.3%) who did not.

Patients receiving the full 6 treatment cycles had a CR rate of 66.7% and a PR rate of 33.3%. Patients receiving 4 cycles of treatment had a CR rate of 33.3% and a PR rate of 57.1%. Additionally, 4.8% of patients who received 4 cycles of treatment reported disease progression, and 4.8% had SD. Among patients treated for 2 cycles, investigators reported a PR rate of 68.2%, a CR rate of 27.3%, and and SD rate of 4.5%.

The first-line treatment comprised 6 cycles, with each cycle lasting for 3 weeks. On the 0th day of the treatment cycle, a 375-mg/m² dose of rituximab was given intravenously, as well as a 750-mg/m² dose of cyclophosphamide and a 70-mg/m² dose of epirubicin (Ellence). On the first and fourth days, a 1.3-mg/m² dose of bortezomib was given subcutaneously, and on the first and fifth day, a 100 mg dose of prednisone was given orally.

The most common grade 1 or 2 adverse effects experienced by 13 patients who completed the 6 courses of treatment were anemia (73.9%), gastrointestinal reaction (52.2%), thrombocytopenia (30.4%), pulmonary infection (21.7%, with 4.3% having grade 3 or 4), neurotoxicity (87%), and rituximab-related rash (8.7%).

For some patients with B-cell non-Hodgkin MZL, it can be difficult to achieve a CR with the standard treatment, and many patients can relapse quickly. The nuclear factor kappa B (NF-κB) signaling pathway is overly active. Bortezomib works as a proteasome inhibitor interfering with the NF-κBpathway. This interference with the NF-κB pathway is one of the mechanisms through which bortezomib may exert its therapeutic effects in MZL.

Editor's Note: The authors declared no conflict-of-interest disclosures.

Reference

Chu J, Wang H, Yao S, et al. Phase II clinical study of VR-CAP regimen for first-line treatment of marginal zone lymphoma. Presented at: 2023 ESMO Congress. October 20 -24, 2023. Madrid, Spain. Abstract 834P.