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Dr. Tatyana Feldman

2yr
TRANSFORM establishes new SOC in treatment of refractory or relapsed LBCL within 12mo after frontline therapy

Results from the primary analysis of the phase 3 TRANSFORM trial show superiority of lisocabtagene maraleucel (liso-cel) over autologous stem cell transplant (i.e., current standard of care in second-line R/R LBCL). Liso-cel is an autologous, CD-19 directed, 4-1BB CAR T-cell therapy administered in equal doses of CD8+ and CD4+ CAR+ T cells.

Previously reported results of an interim analysis performed at a median follow-up of 6.2 months indicated that liso-cel was more effective than SOC as 2L treatment in patients with primary refractory or early relapsed LBCL.

International investigators presented primary analysis at the 2022 ASH Annual Meeting held December 10-13 in New Orleans.

Researchers randomly assigned 184 patients (1:1) to either the liso-cel or the SOC arms. Patients must have LBCL that relapsed within 12 months or refractory to frontline therapy and be candidates for autologous stem cell transplant. In the Liso-cel arm, bridging therapy with R-ICE/R-DHAP or R-GDP was permitted. In SOC arm, patients who achieved CR or PR after 3 cycles of RICE/R-DHAP or R-GDP received autoSCT. Crossover to Liso-cel was allowed.

In total, 73% were refractory to first-line (1L) treatment and 12.5% had double hit DLBCL. At a median follow up of 17.5 months, the primary endpoint of median EFS was not reached in Liso-cel vs 2.4 months in SOC.

Secondary endpoints were also strongly in favor of Liso-cel: CR 74% vs 43% SOC, mPFS was not reached vs 6.2 months SOC.

While not statistically significant, median OS trended better in Liso-cel (NR versus 29.9 months respectively; HR, 0.724; P = 0.0987); 67% of SOC arm crossed over to Liso-cel. There were 28 patients in the Liso-cel arm and 38 patients in the SOC arm who died mainly from disease progression. No new safety signals were observed.

These results together with ZUMA7 data (Yescarta in second line DLBCL) strongly support the use of CART19 cellular therapy as second line in relapsed refractory DLBCL.

What are your thoughts of these data and of using liso-cel as 2L treatment in patients with primary refractory or early relapsed large B-cell lymphoma (LBCL)? In your opinion, which patients would benefit most from liso-cel? How are you going to choose liso-cel vs axi-cel vs tisa-cel as your product of choice?

  • 2yr
    the data for pfs and efs for liso-cel is impressive in this difficult to treat (primary refractory, double hit) dlbcl population, I still have some concerns about the lack of OS benefit, but as pointed out previously, this may be due to high crossover rate in this population. I would also like to see a cost-effective analysis, since these treatments, although single, are very expensive, and the number of patients eligible could be large enough that a financial burden for our health care system.
  • 2yr
    The data presented here is impressive. I think bone marrow transplant should not be considered standard of care anymore in this setting and Liso-cel should be used whenever possible.
  • 2yr
    This further confirms that cart is the second line preferred treatment option for higher risk 2nd line therapy for DLBCL. Liso has less CRS and ICANs than axi and tisa
  • 2yr
    Higher response rate including complete response and improved pfs should make car-t cell SOC for early relapse lbcl (within 12 months). I am not surprised that OS was not significant given the high cross over rate. I refer to our affiliate tertiary care center and defer to Them on choice of car-t. With that said, given the trend towards OS and improved toxicity profile with liso-cel, it would be my preferred choice.
  • 2yr
    It is going to remove stem cell transplant in near future and will be SOC in 2nd line therapy.
  • 2yr
    pts with large cell lymphoma who relapse with in 12 months have grave pts dont do well with stem cell transplant any way
    wthe the above data.liso cel will be standard of care
  • 2yr
    This is a very concerning population of patients, primary refractory or early progression-not the same population as the ZUMA-7 trial, which did not allow a crossover. The data is still a bit early for definitive analysis but strongly favors liso-cel in this population over autologous transplant. I would encourage my patients in these two categories to proceed to Car T cell-the study does not truly specify WHICH Car T cell product one should use! Also, as mentioned by the other respondents, there remains an issue with manufacturing capacities, manufacturing efficiency and inpatient bed availability.
  • 2yr
    will be standard of care for refractory or early relapsed lymphoma in pts who less aggressive disease and don't require bringing therapy
  • 3yr
    This data is presented reveals that Liso is superior to SOC especially since 67% of patients crossed over into the Liso Tx.
  • 3yr
    Very impressive data in second line refractory setting and also superior to stem cell transplant also data impressive in double HiT lymphoma. Would use Liso and Axi-cel. The choice of the CART cell therapy depends upon the availability at the center where they referred to.
  • 3yr
    Data - very impressive, It's clearly superior to transplant in primary refractory as well as early relapse settings - both Lisocabtagene and Axicabtagene are reasonable choices in this setting. PFS was not reached in this trial with Liso-cel and not sure whether we will able to see OS difference given 67% of the SOC arm crossed over to Liso-cel. The data looks good with Axi-cel. At present time I don't think we have that choice or data to choose one vs the other - whichever patient can get to - one of these would be great. Given the negative BELINDA study results - I would not suggest tisa-cel in primary refractory as well as early relapse settings.
  • 3yr
    Impressive data- finally this is the first (i think) CAR-T trial to show superiority. In DOuble hit it’s very impressive for sure; understanding the toxicity the patients get with aut-HCT- not a bad comparison with CAR-T. Main concern is CAN WE GET CAR-T i for whoever we want ? VERY lIMITED SLOTS, manufacturing failures- can be a pain; auto HCT also comes with collection issues etc; definitely will consider instead of transplant;
  • 3yr
    All CAR-T options would be very reasonable- not certain if there is a most preferred regimen at this time- depends more on the center and availability of the agent. But in early relapsers, it's well-known that CAR-T is much more effective as opposed to late relapsers where auto transplant still has a significant role
  • 3yr
    Data impressive. Several CAR-T options. However, when you refer a pt to a CART center, that center chooses the CART therapy, not the referring onc. We just refer for "CART therapy" and which one the pt receives is not under our control at this time.
  • 3yr
    I have seen data on lisocabtagene before from best of ASH meetings, and it is clearly superior to transplant and may even be better than other CAR-T when looking at CR rates, so I am excited for this product in 2L DLBCL
  • 3yr
    This study helps us in deciding the appropriate treatment for relapsed refractory DLBCL. would refer for these pts for CAR T, Lisocel appears a bit easier
  • 3yr
    2nd line car t cell therapy is the standard of care ,fro pts who can tolerate it ,which one to choose is a matter of availability
  • 3yr
    for high risk, early and refractory relapsers, lisocabtagene maraleucel looks like the agent of choice
  • 3yr
    Data looks very good-will need long term followup-we use mainly Yescarta as our CART choice
  • 3yr
    I would use Breyanzi (or Yescarta) in 2L DLBCL refractory to chemo (<12 mo from treatment end) as opposed to tranpslant.
  • 3yr
    Based on this should be standard of care. However will like to see confirmatory data or another trial. Also long term results.

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