A case will be presented of a male individual who was diagnosed with multiple myeloma at age 59. On
his first line of therapy, the patient received standard-of-care Velcade-Revlimid and dexamethasone
(VRd) that was then changed to Kyprolis-Revlimid-dexamethasone (KRd) followed by ASCT and
standard lenalidomide maintenance until progression. The individual achieved a Complete Response
(CR) but relapsed after 22 months post-transplant, meeting the definition of functional high risk. On
his second line, the patient was treated with Elotuzumab (Empliciti)-Pomalyst-dexamethasone (EPd),
achieving only a Minimal Response (MR) and progressing within 4 months. With rapidly rising
biomarkers, the patient was enrolled onto MyDRUG on his third line. The attraction of an all-oral
regimen was an important factor, especially at a time when his treating clinicians could foresee limited
access to clinics, infusions and cellular therapies given the looming COVID-19 pandemic in the US.
ONCOSEQ molecular profiling identified the presence of an NRAS Q61H mutation with a 56% allelic
fraction (as well as confirmed hyperdiploidy and del13q, del1p, and discovered the presence of a Myc
amplification). The patient was put on arm C1 (cobimetinib) of MyDRUG based on these results.
Treatment was well tolerated with no AEs observed. During the two cycles of single agent cobimetinib
(40 mg) and dexamethasone, the M-Protein and kappa serum Free Light Chain (sFLC) decreased by
30% and 47% respectively and this decrease continued with the addition of the IPd backbone, reaching
89% diminution of the M-Protein (and 91% for the kappa sFLC), a Partial Response (PR) just short of a
Very Good Partial Response (VGPR). At the latest data review, this functional high risk patient had
remained at these low levels of biomarkers and was continuing to respond 12 months after initiation
of therapy.
MyDRUG overall is about one quarter accrued at this point in time and quickly enrolling. Efforts such
as MyDRUG will be important in order to make Precision Medicine a reality for all myeloma patients.
References
1. Shah UA and Mailankody S. Emerging immunotherapies in multiple myeloma. BMJ 2020
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autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple
myeloma but outcomes have improved over time. Leukemia 2018 32(4):986-995.
3. Auclair D, Lonial S, Anderson KC, Kumar SK. Precision medicine in multiple myeloma: are we there
yet? Expert Review of Precision Medicine and Drug Development Personalized medicine in drug
development and clinical practice 2019 Volume 4, Issue 2.
4. Auclair D, Anderson KC, Avigan D, Bianchi G, Biran N, Chaudhry M et al., The myeloma-developing
regimens using genomics (MyDRUG) master protocol. JCO.2019.37.15_suppl TPS8057