Targeting CD19 in Diffuse Large B-Cell Lymphoma - Episode 12


May 7, 2020
Targeted Oncology

Ali McBride, PharmD, MS, BCPS, BCOP: With the L-MIND study coming into light, we have seen the evolution of a combination therapy, moving away from the monotherapy early on. Again, the monotherapy studies with tafasitamab did show efficacy. But the combination here with lenalidomide led to improved outcome in these settings. We’re really looking at tafasitamab being infused.

We have our weekly schedule and then we actually go into a biweekly schedule several cycles into it, with lenalidomide actually dosed on day 1 through day 21 versus the 28-day schedule for this treatment. We had seen the actual outcomes of overall response rate and complete response rate truly go up in those patient populations, so it’s comparable here with our PBR [polatuzumab-bendamustine-rituximab] and in some cases maybe even better because of adverse-effect profile mitigation.

The combination had an improved overall response rate with a good CR [complete response] rate as well. That longer duration, that duration of treatment, really alludes to the facts or the principle of continued outcomes with the tafasitamab plus lenalidomide there as well. That outcome evaluation from overall response rate and complete response rate in those transplant-ineligible patients, and not only that but these patients were 72 years old. They had to actually receive 2 lines of therapy.

We are looking at an older-patient population who may have higher comorbidities for seeing this overall response rate truly impact patient populations in this setting. That follow-up period on there is about 13.2 months from the actual L-MIND study. Again, they had seen this improved overall response rate in patient populations.

With the L-MIND study we had seen a good overall response rate of 60% with a complete response rate of about 43%. In addition, partial response [PR] was about 18%. We saw this improved objective response and also CR- and PR-based responses with therapy. This makes this a key player in that relapsed/refractory diffuse large B-cell setting. That was actually 1 of those key components.

In effect, the other piece of this was the actual low percentage of infusion reactions. Not only did patients have a benefit, a long tolerability for duration of response and also for follow-up, but some of their adverse effects were also minimal. This is looking at the comparison for whom you treat for these patients as well, how that’s selected based on adverse effects. For a lot of our patients tolerating sometimes the polatuzumab BR [bendamustine-rituximab]–based regimen, that peripheral neuropathy can be a weakness there.

We have to address those patients later on, especially if they have diabetes or all the comorbidities as well. We’re always playing off the best option for treatment. Looking at this, not only do we have good options for complete response rates, durable response, and overall response, let alone the CR and PR, but also tolerability clearly was developed as well. One thing we do more is addressing the L-MIND study and looking at how it’s playing into future treatments and mitigating adverse effects.

When we’re looking at a combination of therapy like this, the IV [intravenous] and the oral piece, it makes it a little tough. The reason why is, we have to address adverse effects. Most of the adverse effects that were seen during the study were actually seen with the lenalidomide. That was mostly a rash-based issue, some neutropenia-based issues, and thrombocytopenia. From that standpoint, you have to address how you actually dose reduce that.

That’s the lenalidomide piece, which leads to a dose reduction upon those adverse-effect profiles. We are mitigating that and actually breaking it down between the tafasitamab piece and the lenalidomide, so that’s been a constant discussion across the board. As we see this come into play and really come into the market a little more for our patients with increased access, we’ll have to be addressing a lot more of those issues up front with treatment.

The nice thing is, we’ve been using lenalidomide in this setting as well as other disease states. That’s not something that’s new to us in the clinical setting.

When we’re starting the patient on this combination of therapy, it’s really important to address—specifically in the face of COVID-19 [coronavirus disease 2019], where we want to keep patients in the outpatient setting and remove their inpatient time period—the neutropenia and febrile neutropenia [FN]. That initiative is becoming apparent more and more and is prophylaxing those patients up front.

With the actual febrile neutropenia index in this study with the actual tafasitamab and also lenalidomide, it had a lower than 10% FN risk. If I’m not mistaken, it was actually about 6% in the study for L-MIND, so it’s minimal in regard to less than 10%, which makes it a great option. Even more so, one of the key pieces on this was, since we had older-patient population, if it was that caustic, you’d only expect to have a higher FN incidence. Here, we’ve actually had a lower incidence.

That’s been a key discussion… When we’re looking at these combinations, do we also have to address in the face of COVID-19 how this may actually become a determinate? Looking at neutropenia and thrombocytopenia, some of these can be dose-regulated peripheral neuropathy. There are also some adverse effects like pneumonia and thrombocytopenia with these patients as well. But these are actually mitigated and most likely because of lenalidomide.

We actually just dose reduce those patients too, so looking at that evaluation we talked about the CAR T and PBR [polatuzumab-bendamustine-rituximab] before. The majority of adverse effects are mitigated early on, but that FN piece was actually rather unique when looking at this combination; therefore it’s a key point for those older patients when we’re taking a look at the patient population selected.

Transcript edited for clarity.