myeloMATCH: The Next Revolution in the NCTN

SWOG is leading the study’s screening protocol, and a pre-activation revision is now under final review. This Master Screening and Reassessment Protocol (officially “MYELOMATCH,” all caps) should be activated shortly, with the first three substudies launching simultaneously or in rapid succession just afterward.

myeloMATCH breaks new ground in many ways, not least by assembling a portfolio of substudies to treat patients sequentially through all stages of their AML or MDS. Patients will be screened at diagnosis and assigned to a substudy based on clinical, cytogenetic, and molecular features. As they complete their induction treatment, they’ll be rescreened for possible assignment to another substudy designed for a later treatment stage. And the process may be repeated. And repeated.

Because those newly diagnosed with AML typically need to start treatment quickly, the myeloMATCH team has created an infrastructure to return a patient’s initial screening results and substudy assignment within about 72 hours of when the lab receives their specimens. A key objective of the screening protocol is to demonstrate feasibility – that this rapid initial substudy assignment can be done reliably, accurately, and consistently. On a patient’s subsequent screenings, assay results and substudy assignment will be turned around at a less breathless rate – within 10 days.

Three initial substudies are expected to open with or just after the screening protocol:

• MM1YA-CTG01, led by the Canadian Cancer Trials Group 
• MM1YA-S01, led by SWOG 
• MM1OA-EA02, led by the ECOG-ACRIN Cancer Research Group

Substudies and patient flow in myeloMATCH are structured into several clinical “baskets” that indicate the patient population of interest. The first two of these substudies will enroll younger adults with AML (“younger” than 60 years of age), while the third will enroll adults with AML who are 60 or older, or who are not good candidates for intensive therapy. Other clinical baskets indicate patients with MDS or patients in line for a stem cell transplant or cell-based therapy. 

Substudies are also classed into four tiers, based on patient treatment stage. The three substudies above are all Tier 1, designed to enroll newly diagnosed patients to their initial course of induction therapy. Tier 2 substudies will focus on post-remission treatment, Tier 3 on transplant and other consolidation studies, and Tier 4 on the use of duplex sequencing  to target specific mutations.

More than a dozen additional substudies are now in the pipeline, in various stages of development. Part of the wisdom of the myeloMATCH structure is that leadership of the clinical baskets is shared across the participating NCTN groups, a list that includes the Alliance for Clinical Trials in Oncology, in addition to SWOG, CCTG, and ECOG-ACRIN. In fact, myeloMATCH represents an unprecedented level of pan-NCTN collaboration – it’s truly a glimpse into the future.

Because it won’t always be possible to connect every patient with an appropriate matching substudy at every moment of treatment, the myeloMATCH team has developed the “Tier Advancement Pathway” – a process that allows such patients to move to a physician-chosen standard-of-care (SOC) therapy while remaining enrolled on the MYELOMATCH screening protocol, so that when they complete their SOC treatment, they can be screened once again for potential assignment to a matching substudy in the next treatment tier.

Keeping these patients enrolled and continuing to bank their biospecimens even while they’re on SOC treatment does keep open the patient’s option of joining another myeloMATCH treatment trial. It also makes it possible for researchers to follow the natural history and response of each patient’s disease, from the time of diagnosis through all stages of treatment, for essentially all myeloMATCH participants (and the ultimate goal will be to enroll 5,000 participants). Our understanding of and ability to successfully treat the disease stand to benefit enormously.

While myeloMATCH is the product of efforts by what may quite literally be a cast of thousands (and if it’s not yet thousands, it soon will be), I want to recognize some of those whose contributions have been absolutely vital in bringing the trial to the point of activation. 

Of course, Dr. Harry Erba, our leukemia committee chair, and his fellow co-chair of the myeloMATCH senior science council Dr. Mark Litzow, from ECOG-ACRIN, have been central visionaries in realizing myeloMATCH, as has our colleague at the NCI’s Cancer Therapy Evaluation Program, Dr. Richard Little. 

But SWOG has been home to the screening protocol from the start, and I do want to particularly acknowledge some of the key members of our home team as well. These include the screening protocol chair, Dr. Jerald Radich, and co-chair Dr. Shahanawaz Jiwani, our myeloMATCH statistical leaders Dr. Megan Othus and Anna Moseley, and our project managers, starting with Dani Weatherbee. I want to give a special shout-out to SWOG’s senior protocol project manager for myeloMATCH, Sarah Cantu, whom others on the team have affectionately termed "the GLUE.” 

These are all folks who have now devoted years to myeloMATCH, and I’m so grateful for their commitment and diligence in bringing this to the launch pad. I can’t wait for the final countdown to begin!