Polatuzumab Vedotin Plus Anti-CD20 Monoclonal Antibody and Dexamethasone in Previously Untreated Very Old/Frail Patients with Diffuse Large B-Cell Lymphoma
Authors: Yun Xiaoya , Bai Jiefei , Feng Ru , Li Jiangtao , Wang Ting , Yang Yazi , Yin Jingjing , Qian Long , Ding Weidong , Xue Xiaoxuan , Qin Haoyu , Jing Hongmei , Liu Hui 
Published: December 2024

Introduction
For previously untreated patients with diffuse large B-cell lymphoma (DLBCL) who aged over 80 years or classified as frail group by comprehensive geriatric assessment (CGA), R-miniCHOP is the standard regimen. However, due to severe comorbidities and poor physical status, about 50% of them cannot tolerate the R-miniCHOP therapy. Consequently, the median overall survival (OS) of the patients was only 1.3 years. Polatuzumab Vedotin (Pola) has been demonstrated its efficacy and safety in both newly diagnosed and relapse/refractory (R/R) DLBCL patients. In the study, Pola in combination with anti-CD20 monoclonal antibody and dexamethasone (Pola-RD) was explored its effectiveness and safety in very old/frail patients with previously untreated DLBCL. Here we present the characteristics of nine patients and preliminary results.
Methods
The single-center, prospective, single-arm and observational study is conducted by Beijing Hospital. Previously untreated patients with DLBCL aged ≥80 years or aged between 70 to 79 with CGA as frail were enrolled in the study. Participants received up to six 21-day cycles of Pola-RD therapy: Pola 1.8 mg/kg IV day 1, anti-CD20 monoclonal antibody (rituximab 375mg/m2 IV, or Obinutuzumab 1000mg IV day 1), and dexamethasone 15mg QD day1-5, followed up to two cycles of anti-CD20 monoclonal antibody ± dexamethasone regimens. Whole-body 18F-FDG PET/CT scan was scheduled every 3 cycles. Patients who were assessed as stable disease (SD) or progressive disease (PD) would withdraw the study. The primary endpoint is overall response rate (ORR). The secondary endpoints are 1-, and 2-year OS and progression-free survival (PFS), and safety. The treatment response was assessed by 2014 Lugano response criteria. Adverse events were graded by CTCAE 5.0. Patients' enrollment is ongoing.
Results
There were nine patients enrolled in the study from May, 2023 to May, 2024. Of the patients, 2/9 was male, and the median age was 80 years (77-86), with seven patients aged ≥80 years. Among them, 4/9 (44.4%) was classified as non-GCB type according to cell of origin. All of the patients were assessed as stage Ⅲ to Ⅳ by Ann Arbor staging system, and had an International Prognostic Index (IPI) score of 2 or more. Six of the patients received Next Generation Sequencing (NGS), and three of them (50.0%) had TP53 mutation. Patients presenting with gastrointestinal symptoms as their initial manifestation were not administered dexamethasone during the first cycle of treatment. With the median follow-up of 7 months (1-11), eight patients were evaluated for interim response, and five could be evaluated for the efficacy after six cycles of therapy. After two or three cycles, the complete response rate (CRR) was 37.5% (3/8), and the ORR was 87.5% (7/8). After six cycles, the CRR was 60.0% (3/5), and the ORR was 80.0% (4/5). The most common adverse events (AE) were the hematological toxicity. Neutropenia at grade 3-4 was observed in 33.3% (3/9) of the patients. No cases of anemia or thrombocytopenia of grade 3-4 were noted. Lung injury was recorded in 33.3% (3/9) of the patients, and one of them was considered as pola-related. Infection occured in 33.3% (3/9) of the patients, and two of them was grade 3. Cardiovascular events presented in 33.3% (3/9) patients, and one of them was at grade 4. Gastrointestinal events were present in 33.3% (3/9) of the patients, and none reached grade 3-4. Peripheral neuropathy was not observed among the nine patients. Among the patients, 4/9 patients complete the therapy; 2/9 are still in the process of treatment. One of them withdrew the due to pola-related lung injury after 3 cycles of therapy. One patient discontinued the therapy due to the progressive disease after 6 cycles of Pola-RD regimens. Notably, A 72-year female, with a history of coronary stent implantation, hypertension, and cerebral infarction, was enrolled in the study. Within the 2 cycles of pola-RD regimens, she experienced an acute myocardial infarction and severe heart failure, and was subsequently evaluated as stable disease. However, the patient ultimately showed no improvement and was discharged automatically.
Conclusions
Pola-RD may be an effective and well-tolerated therapeutic approach for very old/frail patients with DLBCL. Ongoing treatment and follow-up of the patients will be further updated. More patients are in recruitment.