Real-World Experience of Pola-R-CHP Therapy in Diffuse Large B-Cell Lymphoma Aged 80 or Older

Background

The POLARIX trial reported the progression-free survival superiority of Pola-R-CHP [polatuzumab vedotin (Pola), rituximab, cyclophosphamide (CPA), doxorubicin (DXR), and prednisolone] as compared with that of R-CHOP (rituximab, CPA, DXR, vincristine, and prednisolone) in previously untreated diffuse large B-cell lymphoma (DLBCL) patients (pts) aged 18-80 years. However, the optimal management for very elderly pts who were 80 years of age or older, including the validity of the Pola-R-CHP regimen, still remains unclear. We examined the efficacy and safety of Pola-R-CHP therapy in real-world clinical practice across all-age populations, including a certain proportion of pts aged 80 or older.

Methods

We retrospectively analyzed DLBCL pts who were over 18 years of age and treated with Pola-R-CHP as a first-line regimen from August 2022 to May 2024 at seven tertiary institutions of the Gifu Hematology Study Group. To verify the difference in the distribution of initial dose intensity (IDI) between pts <80 years and pts ≥80 years of age, we created density plots for the IDI of each chemotherapy agent. The multivariable logistic analysis for the factor associated with the occurrence of severe adverse events (sAE) focusing on the non-hematological toxicity and febrile neutropenia was also performed.

Results

A total of 172 pts were enrolled, and the median age at diagnosis was 73 (range 31-93) years. Forty-four (25.6%) pts of whom were 80 years or older at the time of diagnosis. The background factors, except for age, including sex, the frequency of bulky mass, International Prognostic Index, and serum soluble interleukin-2 receptor level, were not significantly different between pts <80 years and pts ≥80 years of age. The median duration of observation was 8.5 (range 0.27-21.8) months. Among the 125 cases in which treatment response was evaluated, the overall response rate between pts <80 years and pts ≥80 years of age has no significant differences (97.8% vs 93.9%, P = .0150). There was no significant difference in the occurrence of sAE between pts <80 years and pts ≥80 years of age (28.9% vs 40.9%, P= .0189), but the treatment-related mortality rate was significantly higher in pts ≥80 years of age than in pts <80 years (11.4% vs 2.3%, P = 0.027). Of the 121 pts who responded, 5 had relapsed. During the observational period, 13 pts (7.6%) died, 2 (1.2%) of whom died of lymphoma, 3 (1.7%) of other diseases, and 8 (4.7%) of sAE. IDI of each chemotherapy agent was significantly lower in pts ≥80 years than in pts <80 years of age (P < 0.01 for DXR and CPA, and P = 0.012 for Pola).

According to density plots illustrating the distribution of IDI for each chemotherapy agent, the shapes of the distribution curves were clearly different between pts ≥80 years of age and pts <80 years. In pts <80 years of age, ADR and CPA had bimodal distributions with a low peak at an IDI of 70% and a high peak at an IDI of 100%, while Pola had a single high peak at approximately an IDI of 100%. On the other hand, in pts ≥80 years of age, ADR and CPA had bimodal peaks at lower IDIs (50% and 70%), whereas Pola still had a high peak at an IDI of 100% with a low peak at an IDI of 50%. The multivariable logistic analysis revealed that worse performance status (PS), lower IDI of average DXR and CPA, and higher IDI of Pola were significantly associated with the occurrence of sAE, rather than age.

Conclusion

Our clinical experience demonstrated that elderly DLBCL pts aged 80 or older who received the Pola-R-CHP regimen had comparable efficacy. Using density plots, we visually revealed that Pola was able to maintain a higher dose intensity than DXR or CPA even in pts aged 80 or older. Although the incidence of sAE did not significantly differ from that of younger pts, the frequency of treatment-related mortality was higher in the older group despite the reduced IDI. The factor influencing sAE was not the age itself, being 80 years or older, but the initial dosage of each chemotherapeutic agent or PS, a most well-known pts-dependent factor. It will be necessary to accumulate more cases to determine the appropriate dosage of the Pola-R-CHP regimen for elderly pts and to establish optimal management strategies for this vulnerable age group.

Kanemura:Sanofi: Honoraria; Novartis: Honoraria; Pfizer Japan Inc.: Honoraria; Asahi Kasei Pharma Co., Ltd.: Honoraria; AstraZeneca K.K.: Honoraria; Bristol-Myers Squibb K.K.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; AbbVie GK: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria. Fukuno:CHUGAI PHARMACEUTICAL CO.,LTD.: Honoraria. Nakamura:Chugai Pharmaceutical Co., Ltd.: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria; Abbvie: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; MSD: Honoraria; Sumitomo Pharma Co., Ltd.: Honoraria; Nippon Kayaku Co., Ltd.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Meiji Seika Pharma Co., Ltd.: Honoraria; AstraZeneca K.K.: Honoraria. Suzaki:Janssen Pharmaceutical: Honoraria.