Patient Selection for ADCs in First-Line DLBCL

Transcript

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Dr. Leonard:
This is CME on ReachMD, and I’m Dr. John Leonard from Weill Cornell Medicine and New York-Presbyterian Hospital in New York. Here with me today is my colleague, Dr. Sarah Rutherford, also from Weill Cornell and New York-Presbyterian. Let’s dive right in. Dr. Rutherford, how do we select patients for regimens containing antibody-drug conjugates in first-line diffuse large B-cell lymphoma, or DLBCL?

Dr. Rutherford:
As you may know, polatuzumab vedotin has now been listed as a preferred combination with R-CHP for frontline treatment of diffuse large B-cell lymphoma in addition to our standard R-CHOP regimen. So when I decide if this newer treatment is appropriate for a patient, I would look at the inclusion criteria of the study, POLARIX study, and I would see if my patient may be one who would’ve fit criteria for that study. So that included ages 18 to 80, IPI [International Prognostic Index] scores of 2 to 5, and ECOG performance statuses of 0 to 2, and then I would look particularly at some of the subgroups that benefited in the POLARIX trial – those patients who were older than 60, male patients, those with IPI scores that were particularly high of 3 to 5, and then also those with the activated B-cell subtype or non-germinal center subtype of diffuse large B-cell lymphoma did appear to benefit more from this regimen. I do want to note that we have had R-CHOP available for a long time, and it is a well-tolerated regimen, and so while I am excited about this new treatment option for patients, and I plan to discuss it with many of my patients who would fit the criteria for the study, I do think that R-CHOP will remain a treatment that we will want to go to for some patients, and I look forward to having this additional discussion with patients as we have another option for them now.

Dr. Leonard:
Thank you. Yes, I agree with much of what you just said. I think that certainly there was evidence, as you alluded to, that there might be benefit in certain subgroups or particular benefit or more benefit in certain subgroups, such as the older patient population, IPI 3 through 5, those without bulky disease, as well as those patients who have the activated B-cell subtype of DLBCL. Why that would be the case, I think, is not entirely clear, but one might argue to at least more strongly consider this regimen in those subgroups of patients. I think other people would take the position that if a patient fell into the category of eligibility for the study, that in the context of an overall positive study, that it would be reasonable to consider for anyone falling into the particular eligibility criteria used for the POLARIX trial. 

I think the other important issue and area that the audience should know about is that there were really insufficient numbers of patients who had double-hit or triple-hit lymphoma, and so I don’t think we can draw these conclusions for that subset of patients. I also agree with you that R-CHOP remains a very important regimen in the absence of an overall survival benefit. Certainly, considering R-CHOP for some patients is still a very reasonable consideration, but I think for most patients, given the fact that there was minimal extra toxicity, perhaps a little bit more febrile neutropenia with the polatuzumab-containing arm, that in the context of a comparably tolerable regimen with an improved PFS, that certainly thinking about the, a polatuzumab-including regimen would make a lot of sense. 

Well, this has been a great discussion. Unfortunately, our time’s now up. Thanks very much for listening.

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