Tandem Meetings 2023 | Lymphoma & myeloma abstract highlights: LV20.19 CAR-T in MCL, Pano/GemBuMel in R/R myeloma & more

So it was an exciting session of lymphoma and myeloma abstracts, a session at Tandem. So there were many interesting abstracts, a few of them to note.

In that session we discussed Dr Shah’s CD19.C20 CAR-T therapy in mantle cell lymphoma. This was a study that was a single center study, Phase I run-in with a Phase II. It was a small study of 11 patients, but this dual targeting CAR-T demonstrated a response rate of about 100%, and at day 90, 92% of patients achieved a CR. So this is really exciting responses. They had a median follow up of about two years, and in that two year follow up, one patient had relapsed. So really promising data though. Of course, small sample size. In terms of safety for this product, all patients had Grade 1 to 2 CRS, but no Grade 3 CRS or higher. And two patients at ICANS, and one of them had disease involvement in the CSF, so that may have correlated as well. So overall, I think this data demonstrated dual targeting C19.C20, CAR-T therapy can be very promising and effective in mantle cell lymphoma with very favorable toxicity profile. And Dr Shah in a separate abstract session also presented data in DLBCL, which I won’t get into, but this was a mantle cell that was presented in the lymphoma myeloma session that I shared. So that was an interesting abstract.

And then we had another abstract that was evaluating safety and efficacy of new high-dose chemotherapy regimen of panobinostat, Gemcitabine, busulfan, and melphalan with autologous stem cell transplant. And this was for patients with high-risk or relapsed/refractory myeloma.

And they evaluated patients that received Pano/GBM for both patients who received frontline transplant as well as transplant in the relapsed setting that were for the first time, as well as a cohort that were receiving transplant for a second transplant. And found that this Pano/GBM was safe and effective in patients with high-risk relapsed/refractory myeloma, particularly after transplant in the frontline setting or for salvage auto transplant. And they compared the cohort with patients who were matched and received melphalan and found that there were improved sort of outcomes in this cohort compared to the matched concurrent control. So I think that was an interesting study. There were a lot of questions raised about should we be intensifying conditioning therapy or not. And the future of the regimen is still unclear given the withdrawal of panobinostat. So it’s unclear where the study would go next, but I think it was interesting results.

And then in lymphoma, which is what I focus on, there was a study presented by Dr Desai, large multicenter study evaluating about 950 patients with relapsed/refractory Hodgkin lymphoma, who received a variety of salvage therapies prior to transplant and they evaluated outcomes of the chemo-based salvage therapy, BV-based salvage therapy or PD-1 blockade-based salvage therapy and found that basically patients who received PD-1 blockade-based salvage therapy had a statistically significant improvement and higher EFS and improved two year PFS compared to chemotherapy or BV alone or BV plus chemo. So I think this study, which was a large sample size and a robust data collection, showed the efficacy improves with using PD-1 blockade and salvage therapy. There was no data on safety. So there is a thought that incorporating PD-1 blockade into salvage regimens can increase the risk of engraftment syndrome, that was not looked at. But I think in terms of efficacy we’ve now seen several studies that have really highlighted the use of PD-1 blockade in the salvage regimen prior to transplant can really improve outcomes post transplant and even in multiply relapsed patients. So I think that kind of highlighted that concept again that we’ve seen. And the common PD-1-based blockade therapies that we now use in combination with chemo tends to be either pembro plus GVD or nivo plus ICE. So those are I think, very good salvage regimens to consider for prior to transplant. So I think that was an important abstract that was presented.

And then there was another abstract in a session that was in myeloma. It was Dr Surbhi Sidana presented the safety and efficacy of ide-cel in relapsed/refractory myeloma patients with renal impairment. And this is a particularly important question because these patients are high risk and we often see in myeloma, these patients with myeloma often have kidney involvement and kidney disease and they’re excluded from a lot of the pivotal trials including the KarMMa trial. So this study particularly looked at patients with renal insufficiency with creatinine clearance less than 50 and over 50 and then a subgroup of creatinine clearance less than 30. And the study found that really outcomes were pretty comparable in patients with renal insufficiency and without renal sufficiency who underwent ide-cel, similar rates of CRS and neurotox. The one thing that they did note was that one month, any grade three or higher cytopenia was more common in those patients with renal insufficiency. And grade three neutropenia and thrombocytopenia were also higher and statistically significant at that one month but became lower at 90 days. So I think the study highlighted that patients with renal insufficiency can have good efficacy outcomes with ide-cel, good safety outcomes with the exception of maybe higher rates of cytopenias at one month.

And really the study also evalued risk factors for patients in terms of renal insufficiency outcomes and found that patients who had high risk disease, prior BCMA, age younger than 65, very independent adverse prognostic factors as we would expect, but renal insufficiency was not. So I think patients with insufficiency should be included in trials, and this is a high risk patient population of unmet need. And the study highlights that really ide-cel can be safe and effective in these patients. So I think that’s the main, I would say the abstracts. And there’s couple others as well, but that’s, in the interest of time, I would say in some of the highlights of the session.