SILVER SPRING, MD – The Food and Drug Administration’s approval this spring of polatuzumab vedotin-piiq, marketed as Polivy by Genentech, Inc., for diffuse large B-cell lymphoma (DLBCL) has special significance for the VA because of its older population of patients.
The FDA approved the drug with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult patients who have previously untreated DLBCL, not otherwise specified (NOS), or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index (IPI) score of 2 or greater.
DLBCL is predominantly diagnosed in the elderly with a median age of diagnosis approaching the 70s, according to a VA study published in 2020. “The prognosis for DLBCL has improved for all age groups, but less so for those over 75 years of age,” wrote authors from the South Texas Veterans Health Care System in San Antonio and colleagues. “The VHA (Veterans Health Administration) is one of the largest integrated providers of cancer care in the United States and its population, on average, is older than the general US population, giving us a unique advantage in exploring outcomes in the elderly population.”
FDA approval with an orphan drug designation was based on POLARIX, a randomized, double-blind, placebo-controlled trial in 879 patients with previously untreated large B-cell lymphoma and an IPI score of 2-5. The trial published in the New England Journal of Medicine was designed to evaluate the superiority of substituting polatuzumab vedotin for vincristine in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen.1
Patients with newly diagnosed DLBCL were randomized (1:1) to receive either polatuzumab vedotin plus R-CHP (pola + R-CHP) or R-CHOP for six 21-day cycles, followed by two additional cycles of rituximab alone in both arms. The main diagnoses were de novo DLBCL, NOS (84%) and high-grade B-cell lymphoma (11%).
Progression-free survival was found to be statistically significantly longer in the pola + R-CHP arm, with a hazard ratio (HR) of 0.73 (95% CI: 0.57, 0.95; p = 0.0177). That arm also had a statistically significant improvement in modified event-free survival (HR 0.75; 95% CI: 0.58, 0.96; p=0.0244). The researchers observed no significant difference in complete response rate or overall survival (HR 0.94; 95% CI: 0.67, 1.33 on the final analysis), however.
The recommended dose of polatuzumab vedotin is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles in combination with R-CHP. The FDA cautioned that patients should be premedicated with an antihistamine and antipyretic and receive prophylactic granulocyte colony-stimulating factor.
In the earlier study published in Blood, VA researchers reviewed, 2036 medical records on patients that had a diagnosis code of some form of lymphoma between 2011 to 2017. Patients were randomly selected. Inclusion criteria were any veteran with at least one entry in their records of selected ICD-9 and ICD-10 codes for lymphoma, and 971 patients ultimately were included. Data was manually abstracted by trained researchers.2
Of patients meeting inclusion data, 739 (76.1%) were younger than 75 years old and 232 (23.9%) were older than 75. “Larger number of veterans were diagnosed at Stage III-IV (67% in <75 years and 67.7% in ≥75 years, p=0.76) with higher IPI score >3 (50.1 % in <75 years and 60.4% in ≥75 years, p=0.0005),” the study pointed out.
The younger cohort received more lines of chemotherapy, i.e. 2 or more lines of treatment (8.9% vs 2.6%), while the older group was more likely to have no treatment or non-chemo treatment (15.5% vs 3.9%).
“For those who received chemotherapy, 82.4% in <75 years vs 76.3% in ≥75 years completed at least 4 cycles of therapy (p=0.07),” the VA authors wrote. “However, 1 year, 2 years and median OS, was statistically different between the two age groups for all three measurements (p<0.0001) and survival decreases as age at diagnosis increases.”
The study pointed out that nearly a fourth of the patient population was older than 75 “ and despite receiving comparable lines of chemotherapy, had lower survival when compared to patients who were <75 years.”
- Tilly H, Morschhauser F, Sehn LH, Friedberg JW, et. al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. doi: 10.1056/NEJMoa2115304. Epub 2021 Dec 14. PMID: 34904799.
- Ananth S, Williams MH, Williams R, Blaize JP, et. al. Impact of Age on Treatment and Outcome in Newly Diagnosed DLBCL (Diffuse Large B-cell Lymphoma) Patients in the United States Veteran Population (2011-2017), Blood, Volume 136, Supplement 1, 2020, https://doi.org/10.1182/blood-2020-143206.