2019 MRD Meeting in NYC

October 2 marked the 6th consecutive year of the Advances in Minimal Residual Disease Testing (MRD) in Myeloma roundtable meeting, a collaborative effort between Memorial Sloan Kettering Cancer Center and the MMRF. This meeting is a yearly opportunity for the myeloma community to come together to discuss the use of MRD testing in clinical practice and the progress toward its acceptance (by FDA) as a surrogate clinical endpoint for myeloma clinical trials.

Attendees are a cross-section of the myeloma community, including leading myeloma physicians, pharmaceutical company representatives, scientists, and this year, for the first time, patient representatives.   All of them came prepared to debate a number of topics related to MRD measurement in myeloma. In each session, audience opinions were assessed before and after the presentations to determine if the arguments succeeded in changing these opinions.



Session 1 featured a debate on the use of MRD testing as a guide in making decisions on whether to perform autologous stem cell transplant (ASCT) in all transplant eligible newly diagnosed myeloma patients up front, or to wait. Initial audience polling before the debate indicated that the majority of attendees felt that MRD should be used for this purpose.

Takeaways:

  • The argument in favor was bolstered by data presented from the IFM 2009 study which indicated that a 4 drug induction therapy which induced MRD negativity offered high risk patients a similar survival benefit to upfront ASCT.
  • The counterpoint argument pointed out that the IFM study followed only a few high risk patients, and that despite the improved efficacy of the new quadruple regimens, ASCT still offers the best survival to the most patients.
  • The final point made was that ASCT up front offers more benefit to the young, high-risk, fit patient than to a 70-year-old standard risk patient, where the best course of action might be up front quadruple therapy and stem cell collection for later transplant if necessary. This latter argument swayed the audience and final polling indicated that it won the debate.

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The debate in Session 2 was around whether MRD should be used to guide how long maintenance therapy should continue after initial therapy and achievement of MRD negativity. Initial audience polling was evenly split on this topic.

Takeaways:

  • The argument for use of MRD for this purpose centered around achievement of sustained MRD negativity for at least 2 years on maintenance, at which point therapy could be discontinued, while MRD and other testing would still be used at regular intervals to closely monitor disease status and catch relapse early so that patients could return to therapy sooner, when it is easier to get myeloma back under control.
  • The counter argument, which stated that MRD was not ready to be used as an endpoint for maintenance therapy due to difficulties in accurate measurement, and uncertainty is when measurements should be made, did not sway the audience, and the “yes” argument prevailed.

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Next, during a working lunch, co-chair Dr. Ola Landgren of MSKCC spoke with Dr. Nicole Gormley of the US FDA regarding an update on the FDA’s perspective on use of MRD as a surrogate clinical trial endpoint. In stating that MRD testing is not yet at the point in myeloma where it might be used as a surrogate endpoint, Dr. Gormley mentioned issues such as:

Takeaways:

  • The threshold at which MRD would be considered truly negative.
  • The amount of time patients would need to sustain MRD negativity at an endpoint.
  • The heterogeneity of myeloma in each patient must be taken into account. As others in the audience mentioned, MRD being used as an endpoint in ALL required 10 years of rigorous testing.

The third debate session, after lunch, centered on the use of MRD to guide when to start 1st relapse treatment. Initial polling indicated that the audience felt that MRD should not be used in this determination.

Takeaways:

  • The “pro” argument listed the fact that conversion of MRD negative to positive (evidence of increased disease burden by a sensitive test such as MRD) is as bad as never having gained MRD negativity, and that in 2019 this conversion, as it correlates with immunochemical relapse and the need for a new treatment, should not be ignored.
  • The counter argument held that too many questions remain regarding exactly when such testing should occur, which patients were the best candidates, and which methodology to use to perform MRD testing., and the audience agreed that MRD should not necessarily be used for this purpose.

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The final session of the meeting consisted of a four patient panel, who each spoke on their myeloma journey and then were asked to weigh in on several questions facing the myeloma community.


In summary, at the end of the workshop, attendees agreed that:

  • ASCT still has a role in myeloma treatment, and that MRD testing may be relevant as a way to help determine when ASCT should be done in individual patients, particularly those with high risk disease.
  • MRD should be used during maintenance therapy to help determine when to stop therapy and start a new therapy.
  • MRD may not be ready for use as a decision point regarding when to begin therapy at first relapse.
  • Having patients give their perspective in these discussions is hugely beneficial to all and helps keep the myeloma community focused on the most important questions that need to be answered.
  • Using a debate style format is an effective way to hear all sides of the issues surrounding use of MRD testing in myeloma.
  • The group looks forward to the 2020 meeting to further discuss these issues and hear more about what patients want and need regarding MRD testing.