Episode 078: Management of relapsed diffuse large B-cell lymphoma (DLBCL) - Part 2
In this FINAL episode of our DLBCL series, we build on our conversation from last week, focusing on the management of relapsed DLBCL. If you have not done so already, we recommend you check out Episode 077!
Last week, we discussed Pola-BR as an option for patients with good efficacy for patients who may not be good candidates for CAR-T or autologous stem cell transplant. What other options are there?
We have two other options in this setting:
This is an antibody drug conjugate to CD19 (therefore don’t give to patients who are headed for CAR-T!)
This can be used after CAR-T relapse as well if a repeat biopsy confirms expression of CD19, though BiTE therapy is now preferred after CAR-T relapse in most scenarios
The study that led to its approval was the LOTIS-2 trial
Enrolled patients who had received two or more lines of therapy
Different population than the Pola-BR study
Transplant eligible were allowed
Transformed and high grade lymphoma were allowed
ORR 48% and CR 24%
We have clear activity of this drug but keep in mind the CD19 target
Interestingly, 15 patients went on to CAR-T after loncastuximab therapy and 6 of them had a complete response
Tafasitamab is an antibody against CD19 - but not an antibody drug conjugate
Has antibody dependent cytotoxicity, antibody dependent phagocytosis, and direct cytoxicity
Revlimid enhances NK cell function and improves the antibody dependent cytotoxicity of tafasitamab
This was combination was studied in the Phase 2 L-MIND study
Included patients with 1-3 prior therapies and were not candidates for transplant
Excluded high grade lymphoma, transformed lymphoma, and primary refractory lymphoma
About 50% of patients only had 1 prior therapy
ORR 60% with CR 40%
Response duration of ~5 months for those with a PR
For those with a CR, over 50% maintain the response at 5 years of long term follow up based on a recent presentation at ASCO suggesting a potential curative potential
Caveat is that many of these patients had low IPI and did not have refractory disease
Still promising as this is fixed duration for one year of therapy
We still can’t make any definitive conclusion whether tafastimab + lenalidomide, loncastuximab, or Pola-BR would be preferred for these patients as the inclusion criteria were significantly different
What is the Fellow on Call approach?
The tafasitamab + lenalidmoide data has shown the longest durable responses with the limitation of a much more favorable population so might be good for a later relapse in an older patient not fit for CAR-T
Loncastuximab was tested in heavily pretreated patients and would be a reasonable option post CAR-T or those with more aggressive disease
Pola-BR can be used as a bridge to something like CAR-T if we are worried about CD19 down regulation with the other options but in that case there is a reasonable argument to just consider Pola-R to prevent poor lymphocyte collection though Pola-BR would be acceptable
R-GemOx is pretty well tolerated and can be an option as a bridge to something like CAR-T or BiTE therapy if needed
How do we approach a patient who has relapsed disease AFTER CAR-T therapy?
Consider repeat biopsy
If disease still has CD19 expression, agents like loncastuximab or tafasitamab + lenalidmoide are still options
It there is not CD19 expression, then want to think about CD20 BiTE therapy.
Current BiTE options (October 2023)
Epcoritamab which is indefinite therapy
Glofitamab which is fixed duration for 12 cycles lasting 21 days each
Note: Both products require step up dosing for the first cycle (weekly therapy)
Subcutaneous injection
Phase I/II study called EPCORE published in April 2023
Most patients had primary refractory disease and about 40% had prior CAR-T
ORR ~60% with CR rate of ~40%
Grade 1 or 2 CRS occurred in about 50% of patients
ICANS was uncommon only in 6% of patients
There seems to be a durable response to therapy for over one year though longer follow up is needed
IV infusion
Phase II study published in NEJM in December 2022
Patients had pretreatment with obinutuzumab to help mitigate CRS
Similar high risk patient population with many patients having prior CAR-T or refractory to CAR-T therapy
Similar CR rate of ~40%
Similar toxicity profile in terms of CRS and ICANS
There also seems to be a durable response to therapy for some patients
Major advantage is the fixed duration of therapy
Bottom line:
BiTE therapy is incredibly promising
Does not require leukapheresis like CAR-T and may ultimately prove to be more efficacious in the future
Our recommendation: Would definitely move to BiTE after CAR-T relapse if the patient could tolerate it
If a patient gets BiTE and achieves a CR, do we proceed with allogeneic stem cell transplant?
Nobody knows at this time but you should consider consolidation with allogeneic transplant after CAR-T relapse. Data are still coming!
This was previously the only curative option after autologous relapse prior to CAR-T
In the modern era, it still remains as possibly the only curative option after CAR-T relapse
The role is definitely now in question and BiTE therapy may provide durable responses
At this point, we should still consider allogeneic transplant and have that discussion with the patient even if they respond well to BiTE therapy
Good news is we can still use all of the other options we had discussed as a bridge to allogeneic transplant after BiTE therapy if needed
References:
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2821%2900139-X/fulltext#seccestitle80 : LOTIS-2 Trial for approval of Loncastuximab
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30225-4/fulltext : MIND-2L study for approval of Tafasitamab + lenalidomide
https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e19522 : Long term follow up data on Tafasitimab
https://doi.org/10.1200/jco.22.01725 : EPOCRE study for approval of Epcoritamab
https://doi.org/10.1056/nejmoa2206913 : Study for approval of Glofitamab
The crew behind the magic:
Show outline: Vivek Patel
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Resonate Recordings
Shownotes: Ronak Mistry
Social media management: Ronak Mistry
We are proud to partner with HemOnc.org!
Want to learn more about the trials that lead to the regimens discussed today? What about dosing schedules? See links in the show notes for a link to HemOnc.org
