R-CHOP combined with immunotherapy can improve the SOC of DLBCL

case

A 58-year-old retired teacher presented with complaints of swollen cervical and inguinal lymph nodes, persistent fatigue, night sweats, and unexpected weight loss of 15 pounds over the past 2 months.

• Social/Family History: Married, lives in rural area, grandfather, adult children live in state, occasionally works as a substitute teacher, avid gardener; no family history of cancer
• History: Hypothyroidism (well controlled with levothyroxine)
• Physical examination: palpable bilateral cervical and inguinal lymphadenopathy
• Laboratory results: Lactate dehydrogenase 310 U/L (upper limit 280 U/L); hemoglobin 11.2 g/dL; bilirubin 1.3 mg/dL (upper limit 1.2 mg/dL); all others within normal limits​
• Hepatitis B, C and HIV negative
• Lymph node biopsy: Immunohistochemistry: CD 10+, CD 20+ confirmed diffuse large B-cell lymphoma (DLBCL); Fluorescence in situ hybridization: BCL6, BCL2 and C-MYC rearrangements were negative.
• Imaging: Whole-body PET/CT scan showed colonic wall mobility, the largest lymph node was 3.9 cm, and there was evidence of subcutaneous tissue involvement.
• Brain MRI showed no evidence of pathology.
• Stage: IV; International Prognostic Index (IPI) 3: High risk
• ECOG Performance Status: 0​
• The patient was started on polatuzumab vedotin-piiq (Polivy) and R-CHP (rituximab (Rituxan), cyclophosphamide, and prednisone).

Targeted Oncology: How many cycles of chemotherapy do you recommend patients with DLBCL receive?

Herbert A. Eladat, MD: Another question at the time was (whether to give) 6 cycles versus 8 cycles of treatment, and I can tell you that there really was no advantage to the extra 2 cycles of treatment. 1 Now the standard (treatment) for the chemotherapy backbone is 6 cycles of treatment and we should not go beyond 8 cycles of anthracycline-based treatment.

This is old news, but I want to emphasize that maybe… there is some value in dose intensity and dose density in patients with higher IPI scores. These (older) data are not comparing it to a 21-day cycle, but rather (increased event-free survival), suggesting that dose density may have some value. I would like to caution, however, as this is not a comparison to a 21-day cycle strategy.¹

What data led to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) becoming the standard of care in this field?

The (Phase 3) Alliance/CALGB 50303 trial (NCT00118209) compared dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) with R-EPOCH CHOP. It shows that the results of the two regimes are essentially the same.² However, when you look at their toxicity profiles, in general, dose-adjusted R-EPOCH ends up being more toxic than R-CHOP, so for most patients, R-CHOP remains the standard, according to the consortium data .²

What studies are looking at adding immunotherapy to chemotherapy to treat these patients?

The POLARIX trial (NCT03274492) is a double-blind randomized study, so patients in the experimental arm received R-CHP plus polatuzumab compared with R-CHOP. 3 There was a placebo drug in each arm, so this was a blinded randomized study in that respect. Patients received 6 cycles of basic chemotherapy and immunotherapy, and then to make everything equivalent, everyone received 2 additional cycles of rituximab in cycles 7 and 8 without cytotoxic chemotherapy. The primary endpoint is investigator-assessed progression-free survival (PFS), and secondary endpoints include EFS, overall survival (OS), and safety data. These were patients with previously untreated DLBCL and their IPI score had to be 2 to 5, so they excluded patients with IPI 1. (This was also a) large study involving 879 patients.³

What were the patient characteristics of this study?

The arms are very balanced. Judging from the disease stage at the time of patient enrollment, approximately 90% of the patients in both groups had stage III or IV disease, with a heavy disease burden. Approximately 50% of patients have more than 2 extranodal sites. 3 Approximately 43% of patients in both arms had bulky disease, defined as more than 7.5 cm, and thus (this group shows a) a considerable disease burden. Approximately 62% of patients had an IPI score of 3 to 5.

Then looking at the various cell sources, most patients have a germinal center B-cell-like subtype, while about 30% have an activated B-cell phenotype, and another 10% to 15% are unclassified. Looking at the subgroup of patients with double-expressing proteins and double- or triple-hit histology, approximately 5% to 7% of patients have double-hit histology, and approximately 35% to 40% of patients have double-overexpressed protein histology.³

What is the primary efficacy outcome of this treatment regimen?

PFS did improve (polatuzumab plus R-CHOP) and was statistically significant. 3 HR was 0.73 (95% CI, 0.57-0.95, ask = .02), so this represents a 37% reduction in the risk of disease progression in favor of the polatuzumab plus R-CHP strategy. Among EFS results, there was a similar trend in favor of polatuzumab/R-CHP (HR, 0.75; 95% CI, 0.58-0.96; ask

= .02).As far as operating systems are concerned…(these figures) are not statistically significant ask The value was 0.75 (HR 0.94 (95% CI, 0.65-1.37) when looking at both arms).³

^{refer to}

^{1. Pfreundschuh M, Schubert J, Ziepert M, et al.; German High-Grade Non-Hodgkin Lymphoma Study Group (DSNHHL). Biweekly CHOP-14 treatment with or without rituximab for 6 versus 8 cycles in elderly patients with aggressive CD20+ B-cell lymphoma: a randomized controlled trial (RICOVER-60 ). Lancet Anker. 2008;9(2):105-16. doi:10.1016/S1470-2045(08)70002-0}

^{2. Bartlett NL, Wilson WH, Jung SH, et al. Dose-adjusted EPOCH-R versus R-CHOP as first-line treatment of diffuse large B-cell lymphoma: clinical results from the phase III intergroup trial Consortium/CALGB 50303. Journal of Clinical Oncology. 2019;37(21):1790-1799. Number: 10.1200/JCO.18.01994}

^{3. Tilly H, Morschauser F, Sehn L, et al. Polatuzumab Vedotin is indicated for the treatment of previously untreated diffuse large B-cell lymphoma. New England Journal of Medicine. 2022;386:351-363. doi:10.1056/NEJMoa2115304}