Comparing R-pola-mini-CHP to R-mini-CHOP in elderly or frail patients with diffuse large B-cell lymphoma

As older patients with diffuse large B-cell lymphoma (DLBCL) still face an unmet need for safe and effective treatment options, the POLAR BEAR study aimed to assess R-pola-mini-CHP as compared to the current standard of care R-mini-CHOP as first-line treatment for elderly and/or frail patients with DLBCL. Although the replacement of vincristine with polatuzumab vedotin in R-mini-CHOP was not associated with more grade 3-4 haematological toxicity, risk for infection or neuropathy, it came at the cost of a higher frequency of gastrointestinal adverse events.

Over the past decade, the overall survival (OS) of patients with diffuse large B-cell lymphoma (DLBCL) has significantly improved. However, for patients above the age of 80 years, which represent an increasing proportion of DLBCL patients, safe and effective treatment options are still an unmet need. Therefore, the POLAR BEAR study aimed to assess R-pola-mini-CHP as compared to the current standard of care R-mini-CHOP as first-line treatment for elderly and/or frail patients with DLBCL. Data on safety from the first 127 patients included in the trial were reported at EHA 2023.

Study design

The phase III POLAR BEAR study enrolled patients with newly diagnosed DLBCL who are more than 80 years old or between 75-80 years and frail, according to a simplified Comprehensive Geriatric Assessment. Patients were randomised in a 1:1 ratio to R-mini-CHOP (i.e. standard of care arm) or R-pola-mini-CHP (experimental arm), both for six cycles. Polatuzumab vedotin was administered at 1.8 mg/kg on day 1 of each treatment cycle. A total of 300 patients are planned for enrolment and patients will be followed up to 36 months after end of treatment. All patients have stage III-IV disease and a WHO performance status of 0-3. Reporting of grade 1-2 haematological toxicity was not required according to the protocol.

Results

Between August 2020 and May 2023, 140 patients from Sweden, Norway, Denmark, Finland and Italy were enrolled in the study (standard of care arm, N= 71; experimental arm, N= 69). In total, 18.2% of patients in the standard-of-care arm and 15.9% of patients in the experimental arm were younger than 80 years, and were enrolled due to frailty. At the data cut-off, the safety profile was mostly comparable between the two arms and the majority of adverse events (AEs) were of grade 1-2. More grade 1-2 events categorised as “other” were reported in the experimental arm, but without a clear pattern. There was no difference in the rate of grade 3-4 haematological toxicities between R-mini-CHOP and R-pola-mini-CHP. In terms of infections, there were 10 grade 3-5 events in the R-mini-CHOP arm and 11 events in the R-pola-mini-CHP group. However, gastro-intestinal toxicity of grade >1 was more frequent in the R-pola-mini-CHP arm than in the R-mini-CHOP arm (20.3% vs. 12.7%), including one fatal event of intestinal ischemia, not related to treatment. Most gastro-intestinal adverse events were due to diarrhoea and were usually transient. Seven patients in the R-mini-CHOP and nine patients in the R-pola-mini-CHP groups experienced peripheral neuropathy of grade 1.

Serious AEs were reported in 65% of patients in the R-mini-CHOP arm and 75% of patients in the R-pola-mini-CHP, most serious AEs were due to infections. In total, 27 patients died (lymphoma, N=9; toxicity, N= 2; COVID-19, N= 5: pneumonia N= 3; renal failure, N= 2; pulmonary embolism, N= 1 and unknown causes, N= 5). After a median follow-up of 1.1 years, a two-year PFS rate of 65% was reported for the pooled population. Thus far, no negative impact of age or comorbidities on PFS was observed.

Conclusion

R-mini-CHOP and R-pola-mini-CHP are both tolerable in elderly patients with DLBCL, with no differences in haematological toxicity or peripheral neuropathy. Nonetheless, R-pola-mini-CHP was associated with more gastro-intestinal toxicity, usually transient and most commonly in cycles one and two. Early pooled efficacy data are encouraging.

Reference

Leppä S, et al. Initial safety data from the phase III POLAR BEAR trial in elderly or frail patients with diffuse large cell lymphoma, comparing R-pola-mini-CHP and R-mini-CHOP. Presented at EHA 2023; Abstract S227.