A recent Parade Magazine story by Frank Lalli about a myeloma patient has brought national attention to multiple myeloma. Lori Alf was diagnosed in 2009 at the age of 43. Her journey brought her through a range of treatments including stem cell transplant that couldn't knock down her aggressive myeloma. Within a few weeks of transplant, her myeloma was back. She and her husband Chris started looking for different and unique options - immunotherapies. University of Pennsylvania researcher Dr. Alfred Garfall included Lori in the first UPenn CAR T Cell clinical trial targeting CD19 with stunning results. Lori started myeloma treatment at Dana-Farber Cancer Institute in Boston who started her on lenalidomide, bortezomib and dexamethasone (RVD) to get the myeloma under control before she could start her transplant. After 9 months of RVD and the addition of high doses of Cytoxan, doctors said the strategy wasn't working well. She was admitted to the hospital to receive a combination of dex, Cytoxan, etoposide and cisplatin (DCEP) and then went on to autologous stem cell transplant, but her disease returned within weeks of SCT. According to the Parade article:
...within a week, she and her husband, Chris, took control of what became a seven-year ordeal to keep her particularly aggressive cancer in check. While many myeloma patients find therapies that allow them to enjoy the semblance of normal health for years, Alf lurched from one disappointing treatment to another, including a debilitating stem cell transplant using her own blood. Few therapies helped her for more than months at a time. “I had a really mean cancer,” she says. Her lead myeloma specialist, the renowned Kenneth C. Anderson, M.D., of Boston’s Dana-Farber Cancer Institute, agrees: “Lori had one of the worst myelomas I have ever seen.” By 2014, Alf was down to 80 pounds, with a grim prognosis.
She considered an allogenic transplant, but was worried about the effects of graft vs. host because her sister was not an exact match. She joined a new immunotherapy clinical trial led by Dr. Alfred Garfall and Dr. Edward Stadtmauer based on research by Carl June. The treatment had been successfully used in leukemia and they were trying it for the first time in multiple myeloma. The study had patients first do an autologous transplant and then engineered her T Cells to target a protein called CD19. This protein is commonly found on the surface of leukemia cells, but not on myeloma cells. Because they had used it before and understood its safety profile, they decided to apply it to multiple myeloma. According to Parade:
In a process similar to kidney dialysis, she was hooked up to a machine that collected a type of white blood cells called T cells. “Then the lab made my T cells very angry,” she explains. Actually, the lab transformed the T cells with a protein called chimeric antigen receptor (CAR) into what they hoped would be an army of hunters that would recognize her enemy myeloma cells and kill them. Twelve days later, the doctors dripped the red, garlicky-smelling CAR T cells into her veins. The next day, she felt sicker than ever. But that was about what the doctors had hoped: In their earlier trials with leukemia patients, when the immune system’s army overwhelmed the enemy, the warfare commonly triggered high fevers, nausea, muscle pain and sometimes serious neurological symptoms. Fortunately, Alf was spared the worst of that and was well enough to be discharged a week later to a nearby hotel. Still, she continued to feel “jittery, itchy, twitchy and miserably nauseous.” But her blood tumors decreased—then disappeared.
Dr. Alfred Garfall says even though myeloma cells don't necessarily have CD19 on their surface, he thinks that precursor myeloma stem cells do, which is why Lori had such a dramatic response and lasting effect with the CAR T Cell treatment. You can learn more about the details behind this strategy from our Myeloma Crowd Radio show with Dr. Alfred Garfall. The results for Lori are completely stunning because Lori was already heavily pre-treated (having received over 9 prior therapies) and had had multiple high-risk features, including del17p, one of the most challenging and aggressive myeloma genetic features. The Myeloma Crowd is supporting CAR T Cell Research like this to bring potentially curative solutions to patients like Lori who have high-risk disease. To support this research, create your own page or donate now. UPenn now has a study using CAR T Cells that target a protein commonly found on myeloma cells: BCMA. To learn more about this clinical trial, click here: UPenn's CAR T Cell BCMA Clinical Trial
about the author
Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical research. Founder of HealthTree Foundation (formerly Myeloma Crowd).