Day 1: mAb’s, CAR-T, and Checkpoints . . . oh my!

| Jack Aiello

Oh my indeed, what a very long but exciting day at ASH. It began with a 7:30 a.m. working breakfast of the IMF’s International Myeloma Working Group (IMWG) that consists of more than 200 myeloma experts from around the world (including 17 new members in 2016). One of their tasks is to write consensus guidelines and research papers. In 2016, IMWG published five papers plus have four more are pending. One of the most important was Dr. Shaji Kumar’s consensus guidelines on Minimal Residual Disease (MRD), which coincidentally I saw referenced later in the day during an MRD study.

The IMWG also discussed possible future projects, such as updating smoldering multiple myeloma (SMM) criteria and treatment guidelines for relapsed/refractory (RR) patients. At this point, an interactive discussion followed about the pro’s and con’s of recommending specific treatments versus listing many options. The meeting ended with presenters of some of the top abstracts providing previews of their upcoming presentations as well as taking many questions. In future blogs, I’ll discuss three interesting potential future drugs: Nelfinivar, Venetoclax, and Selinexor.

Later this morning and in the afternoon, I attended Myeloma Immunotherapy Education and Scientific Programs, both discussing the current state of monoclonal antibodies (mAb’s), CAR T-cell therapy, checkpoint inhibitors, and vaccines. Regarding the difficulty of developing mAb’s, Dr James Kochenderfer said “There are no known plasma cell antigens (targets) that have strong uniform expression on multiple myeloma cells, while not being expressed on normal cells.” While multiple myeloma tends to suppress the immune system, checkpoint inhibitors can make the myeloma cell more visible to the immune system. I had heard about the PD1/PDL1 inhibitors (e.g. Pembrolizumab) enabling T-cells to “see” multiple myeloma cells, but until today, hadn’t heard of KIR ligand pathway inhibitors (e.g. Lirilumab) also being developed to enable natural killer (NK) cells of the immune system to be more effective. Interestingly though, these checkpoint inhibitors don’t have much single agent activity in myeloma, but enhance the effectiveness, say, of Revlimid when combined with it. I will blog more about immunotherapy over the next few days.

I attended a few abstract oral presentations today.  One (#242) showed that consolidation after an SCT benefitted standard risk MM patients but not those considered high-risk. Another study (#243) showed that ixazomib + Rev/dex was more effective in RRMM patients who had higher c-MYC expression unless prior treatment included a stem cell transplant. Go figure. Finally, there were a couple of orals (#245, #246) that showed better MRD results correlated with better outcomes, thus further supporting the role of MRD as a primary endpoint and surrogate marker in future clinical trials.

Our myeloma SWOG committee met during lunch. SWOG is one of the four national cancer network groups running primarily Phase 2 and 3 clinical trials. We typically have monthly conference calls so it’s always appreciated when we have the opportunity to meet face-to-face and discuss proposed and on-going trials. To offer a patient’s perspective, I’m a committee member.

In between talks, I checked out posters such as #2123 “Preliminary Results From a Phase 1b Study of Isatuximab in Combination with Pom and Dex in Relapsed/Refractory Multiple Myeloma,” confirming clinical activity for this regimen that includes a new CD-38 mAb. And this evening, I attended the IMF’s annual grants award reception. After listening to some wonderful patient stories, I was encouraged to see young researchers presented with monetary awards to continue their research in areas that will potentially benefit myeloma patients.

That’s it for a long day. Wishing you the best of health.

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Jack Aiello

Diagnosed with myeloma in 1995, Jack is strong proponent of patients participating in clinical trials so that, in the future, myeloma and other cancers will be known as curable diseases. He is a proud facilitator of the San Francisco Bay Area Myeloma Support Group.

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