UH Seidman Cancer Center at ASH 2022

Innovations in Cancer | Winter 2023

Leland Metheny, MD, and Ehsan Malek, MD, from UH Seidman Cancer Center recently shared important research findings at the annual meeting of the American Society of Hematology (ASH) in New Orleans.

Leland Metheny,MD

Dr. Metheny reported on a multicenter Phase I study of post-transplant low-dose intouzumab ozogamicin (INO) to prevent relapse of Acute Lymphoblastic Leukemia (ALL). INO is an anti-CD22 monoclonal antibody bound to calicheamicin and approved to treat relapsed ALL. The primary objective of the trial was to define a post-allogeneic transplant maximum tolerated dose (MTD) of INO. Trial results show that INO at doses of 0.3, 0.4, 0.5 and 0.6mg/m2 was well tolerated and that 0.6 mg/m2 is the MTD. Thrombocytopenia may be the dose-limiting toxicity. The researchers say that the low observed relapse rate and favorable safety profile justify investigating low-dose INO as maintenance therapy after alloHCT in a Phase II trial.

Dr. Malek reported on a tool to longitudinally assess the secretory capacity of multiple myeloma (MM) cells throughout the course of disease. International Myeloma Working Group (IMWG) criteria to assess tumor volume rely on the secretory function of MM cells, determined by the concentration of the circulating monoclonal protein (M-protein) to infer tumor burden.  Hence, changes in M-protein levels may be indicative of therapeutic response or disease progression. IMWG criteria assume that the secretory power of an individual myeloma cell remains constant throughout the course of treatment, but this assumption has not been tested, due to the inability to accurately measure MM cell numbers. However, because Next Generation Sequencing (NGS) now allows for direct measurement of tumor cell number, Dr. Malek and his colleagues were able to develop a method to define a “Secretory Power Index” (SPI) as a longitudinal tool to assess tumor burden. Results with 47 patients suggest that SPI decreases over time as patients go through different lines of therapy. The research team plans to validate this tool in a larger prospective cohort to demonstrate that IMWG criteria could under-estimate the response measured by global secretory function.

Ehsan Malek, MD

Dr. Malek also reported on an artificial intelligence approach to assess the systemic impact of malignant plasma cell clone in patients with plasma cell dyscrasia. End-organ damage is the key factor that differentiates plasma cell (PC) dyscrasia requiring therapy, i.e., active multiple myeloma (MM), from disease precursor stages, i.e., (Monoclonal Gammopathy of Undetermined Significance or MGUS, and Smoldering MM or SMM) that do not require therapy. The prevailing assumption is that MGUS and SMM patients do not harbor significant or measureable systemic impact of clonal PCs. Therefore, a watch-and-wait approach is employed in MGUS and SMM patients until end-organ damage is evident. However, Dr. Malek and his colleagues are exploring the idea that the systemic impact of clonal PCs is a continuum throughout disease progression, rather than a binary process, and that the impact on organ systems correlates directly with the volume of the malignant clone as measured by monoclonal protein levels. Results of a machine learning process with all relevant data from 171 patients show that the degree of systemic involvement induced by the clone correlates directly with magnitude of the machine learning-calculated M-spike value. They say that applying this algorithm in longitudinal studies of patients with MGUS and SMM is warranted to detect the optimal point of multi-systemic impact of clonal PCs to start therapy.

Last, Dr. Malek and colleagues reported on their National Cancer Database study examining whether patients with Smoldering Multiple Myeloma (SMM) diagnosed at a younger age have faster progression to symptomatic MM. The latency period remains largely unknown for the majority of MM patients. Results from 12,984 patients with SMM indicate the rate of SMM to MM progression is independently and inversely associated with age of SMM detection. In other words, early onset of smoldering disease correlates with rapid progression to symptomatic MM. On multivariable analysis, each 10-year decrease in age (OR 1.06, 95% CI: 1.05 – 1.06, p<0.0001), white vs black race (OR 1.02, 95% CI: 1.00 – 1.04, p=0.027), and each 1-year decrease in diagnosis year (OR 1.01, 95% CI: 1.00 – 1.01, p=0.015) were associated with progression to MM, however male vs female gender (OR 1.01, 95% CI: 0.99 – 1.02, p=0.26) was not statistically significant. These findings highlight the potentially longer latency period in older patients, which can denote more indolent disease in elderly MM patients.