R-CHOP Followed by R-ICE Treatment Shows Potential for Patients With Non-GCB DLBCL

Andrew Zelenetz, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses study results that suggest rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by rituximab, ifosfamide, carboplatin, and etoposide ([R]-ICE) may improve overall outcome among patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). 

Transcript:

Hi, I am Andrew Zelenetz, attending physician at Memorial Sloan Kettering Cancer Center in New York, and a member of the Lymphoma Service. Today I'll be discussing our long-term results of a sequential chemoimmunotherapy program of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), followed by ifosfamide, carboplatin, etoposide (ICE) chemotherapy. 

The idea behind this study originally was [an] early introduction of non-cross resistant chemotherapy. Patients received 4 cycles of slightly dose modified R-CHOP. Cyclophosphamide was administered at 1,000 mg/m². Vincristine was uncapped and treatment was given every 2 weeks for 4 doses, and then the patients received 3 cycles of ICE chemotherapy. There was a slight modification in the 2^nd protocol, but fundamentally the treatment regimen was the same.

What we found was that the long-term results were excellent with about 70% of patients remaining progression-free [and] with an overall survival that was in the range of 75% with very long-term follow-up. But when we undertook an analysis of the data, one of the things we noticed was that the patients who had activated B-cell tumors, or non-germinal center tumors, because this was by the Hans model, had an unexpected superior outcome compared to germinal center tumors. 

Now, most studies have shown that non-germinal center large cell lymphoma has an inferior outcome to germinal center large cell lymphoma. But interestingly in this dataset, it was superior for the non-germinal center tumors. We wanted to know if this was a real observation.  We undertook a case match control study using the molecular epidemiology resource of the Mayo Clinic/ [University of] Iowa SPORE, and collaborated with our colleagues at the Mayo Clinic and identified a group of patients that were matched for the key clinical variables and found that as expected, the germinal center tumors did a little bit better than the non-germinal center tumors in their R-CHOP treated cohort.

When we compared to the results from the memorial cohort, in fact, the patients who were treated with the sequential chemo immunotherapy program had a slightly better overall outcome, but really that overall outcome was driven by improvement in the non-germinal center large cell lymphoma. Now we have similar results now from the POLARIX study showing that R-CHP polatuzumab seems to be better in that same group of patients. Though I would argue that sequential R-CHOP followed by ICE is a whole lot less economically toxic than the R-CHP-pola regimen, but both provide actually similar excellent results in this more unfavorable group of non-germinal central large cell lymphoma.

Source:

Bantilan K, Smith A, Maurer J, et al. Matched control analysis suggests R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared to R-CHOP. Blood Adv. Published online January 25, 2024. doi: 10.1182/bloodadvances.2023011408