Discussing Subgroup Responses to Immunotherapy and R-CHOP in DLBCL

CASE

A 58-year-old retired schoolteacher presented with the chief complaint of swollen lymph nodes in his neck and groin, persistent fatigue, night sweats, and unintentional weight loss of 15 pounds over the last 2 months​.

• Social/family history: married, lives in rural area, grandfather, grown children live in state, works occasionally as a substitute teacher, and avid gardener; no family history of cancer
• Medical history: hypothyroidism (well controlled with levothyroxine) ​
• Physical exam: palpable bilateral cervical and inguinal lymphadenopathy​
• Laboratory results: lactate dehydrogenase 310 U/L (280 U/L upper limit); hemoglobin 11.2 g/dL; bilirubin 1.3 mg/dL (1.2 mg/dL upper limit); all others within normal limit​
• Hepatitis B, C and HIV negative​
• Lymph node biopsy: immunohistochemistry panel: CD 10+, CD 20+ confirmed diffuse large B-cell lymphoma (DLBCL); fluorescence in situ hybridization: negative for rearrangements of BCL6, BCL2, and C-MYC​.
• Imaging: whole body PET/CT scan showed activity in colonic wall, largest node 3.9 cm; there was evidence of subcutaneous tissue involvement​.
• MRI of the brain showed no evidence lesions​.
• Stage: IV; International Prognostic Index (IPI) 3; high-intermediate risk
• ECOG performance status: 0​
• The patient was started on polatuzumab vedotin-piiq (Polivy) and R-CHP (rituximab [Rituxan], cyclophosphamide, and prednisone).

Targeted Oncology: What was the reaction to the efficacy data of the POLARIX trial (NCT03274492)?

HERBERT A. ERADAT, MD​: It has generated some degree of controversy, especially in academia, and...the number one question that comes up is about why there was improvement in progression free survival [PFS], but not an improvement in overall survival [OS].1 This was, at least in part, related to the fact that the patients who progress have the option to move on to subsequent lines of therapy. So, when we look at OS down the road beyond this first-line therapy, there doesn't seem to be that much of a difference; [it seems like] polatuzumab vedotin and R-CHP is not making a dramatic change in the biology of the disease since this is not impacting OS.¹ Along with this question, we asked what are the subsequent lines of therapy [patients are going on] and how are they responding? Also, is there a difference between the 2 arms [on this study] in terms of the need for subsequent lines of therapy?

Herbert A. Eradat, MD​

Assistant Professor of Medicine​

Department of Medicine

Hematology/Oncology

Member, Signal Transduction and Therapeutics

UCLA Medical Center

Santa Monica, CA

[The answer is] yes, there were more patients in the R-CHOP arm that needed any subsequent line of therapy [compared with patients on polatuzumab vedotin and R-CHP at 30.3% vs 22.5%, respectively].¹ More patients in the R-CHOP arm also needed radiotherapy [13.0% vs 9.3%] and more patients needed systemic therapy after the R-CHOP transplant [23.5% vs 17.0%]. So yes, there is a need for additional lines of therapy, perhaps beyond the R-CHOP [treatment], but fortunately these patients appear to respond, at least reasonably well, to the subsequent lines of therapy where the OS is not impacted.¹

How do patients with germinal center DLBCL respond compared with non-germinal DLBCL?

The pattern is similar in the sense that the patients who have a germinal center DLBCL subtype still do better than the patients that have a non-germinal center subtype [disease], in terms of the strategy. The addition of the polatuzumab vedotin didn't change that hierarchy.¹ In regard to the use of polatuzumab vedotin in subsequent lines of therapy, that's an open question. I am not aware of data that [suggests a physician could re-treat with polatuzumab vedotin], but theoretically, if you wanted to, it's worth a try. I am just not aware of the data in terms...of what the response rate would be and the durability of any responses if you've already used polatuzumab vedotin in the front-line.

Was there a treatment benefit for patients with double-hit or double-expressor DLBCL?

Based on the data in the POLARIX study, and based on the Alliance/CALGB 50303 trial [NCT00118209] data, R-CHOP seems to be inadequate for patients with double hit DLBCL, even for the double-expressor [patients] too.^1,2 We don't have data establishing that anything is better, but all of us at least try to escalate [treatment], if it's doable, for patients...and perhaps they will get some benefits. That is what we do at [the UCLA Medical Center], and what I'm seeing across the country at various academic centers is a similar pattern. This is primarily based on the fact that the R-CHOP strategy is at least inadequate for this category [of patients]. However, in the POLARIX data, we also didn't see a trend that necessarily showed the addition of polatuzumab vedotin changes the biology for double-expressor, double- or triple-hit DLBCL.¹

^References:

^{1. Tilly H, Morschauser F, Sehn L, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022; 386:351-363. doi:10.1056/NEJMoa2115304}

^{2. Bartlett NL, Wilson WH, Jung SH, et al. Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019;37(21):1790-1799. doi:10.1200/JCO.18.01994}