UH Seidman Cancer Center Faculty Presentation Highlights from ASH 2021 and ASTRO 2021 Annual Meetings

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Innovations in Cancer | Fall 2021

Selected UH Seidman Cancer Center Faculty Presentations at ASH 2021

Epigenetic Priming with Pre-Transplant Oral Panobinostat Followed By Post-Transplant Consolidation

Ehsan Malek, MD, and colleagues from UH Seidman Cancer Center have designed a Phase 1b dose-finding study in multiple myeloma patients employing a pre-stem cell transplant (SCT) epigenetic priming phase with high-dose panobinostat, a histone deacetylase (HDAC) inhibitor, and a post-SCT lower dose panobinostat consolidation phase. Previous studies support HDAC inhibitors in combination with melphalan to augment anti-myeloma efficacy of high-dose melphalan and SCT. Multiple myeloma patients with adequate stem cell collection for transplant will receive one week of high-dose panobinostat before undergoing standard of care high-dose melphalan and stem cell transplant in the epigenetic priming phase, followed by a consolidation phase of six months of fixed-dose panobinostat after transplant.

Mycobiome Supporting Diet to Reduce Gastrointestinal (GI)Toxicity Associated with Autologous Stem Cell Transplant (ASCT) for Patients with Multiple Myeloma (MM)

Multiple myeloma patients at UH Seidman Cancer Center followed a microbiome-supporting diet (MSD) for 28 days on a prospective trial. At the end of the study period, subjects had a 1.7-fold decrease in the abundance of Proteobacteria (considered a red flag for inflammation), with levels reduced from 38.6% to 23.3% with significantly increases of beneficial species. Furthermore, pathogenic bacteria decreased significantly. After the study, all participants with GI symptoms reported moderate or dramatic improvements, while 30% reported moderate or dramatically improved fatigue and higher energy levels. Ehsan Malek, MD, and colleagues are now evaluating the feasibility of MSD diet based on patient adherence, assessed at three, two and one week before transplant. The MSD diet will be deemed deem feasible if at least 80% of patients showed adherence defined by 2 out of 3 assessment marked “more than half a time.”

Post-Transplant Inotuzumab Ozogamicin for Acute Lymphoblastic Leukemia

Leland Metheny, MD, and colleagues from UH Seidman Cancer Center have conducted a Phase I/II study of low-dose inotuzumab ozogamicin (INO) as a post-allogeneic HCT strategy to prevent relapse in acute lymphoblastic leukemia (ALL). Eligibility included patients age 16-75 who have undergone alloHCT for CD22+ALL in complete remission, have a high risk for relapse after alloHCT, have adequate graft and organ function, are between day 40 and 100 post-alloHCT, do not have active grade III/IV GVHD or any active GVHD of the liver, and have no history of veno-occlusive disease. After one year post-alloHCT, 11 of 12 patients are alive and in complete remission at 12 months from last dose of INO. In the phase 1 portion of this study, INO at doses of 0.3, 0.4, 0.5 and 0.6mg/m2 was well tolerated. Thrombocytopenia may be the dose-limiting toxicity. Given the low observed rate of relapse, along with the safety profile, investigation of low-dose INO as maintenance therapy after alloHCT will be continued in a phase II trial.

Selected UH Seidman Cancer Center Faculty Presentations at ASTRO 2021

International Meta-analysis Quantifies Impact of Three Prostate Cancer Therapy Intensification Strategies

An individual patient data (IPD) meta-analysis of randomized, controlled clinical trials provides strong evidence for the addition of androgen deprivation therapy (ADT) to definitive radiotherapy (RT) for the treatment of prostate cancer, with the projection that adding ADT to the treatment of 10-15 men would prevent the development of distant metastasis in one man. Similarly, if ADT has been added, prolonging the portion of it that follows the radiation (called “adjuvant ADT”) to 18-36 months provides a similar benefit in terms of preventing metastatic disease. The benefits of adding ADT and of prolonging adjuvant ADT were identified regardless of patient age, RT dose (high vs. low), or prostate cancer risk group (high vs. intermediate risk). In contrast, prolongation of ADT that begins before radiation (called “neoadjuvant ADT”) beyond two to three months did not improve any cancer outcome, according to the study, prompting researchers to conclude that the latter treatment should not routinely be employed. The analysis was conducted thorough the Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium, a group formed in 2020 to serve as a data repository from international trial groups by Amar Kishan, MD, associate professor and vice chair of clinical and translational research in the department of Radiation Oncology at UCLA, and Daniel Spratt, MD, the chairman of the Department of Radiation Oncology at University Hospitals Seidman Cancer Center. The MARCAP consortium has data from multiple trials across the world and is the first consortium group of its kind for prostate cancer.

Pan-Cancer Analysis of Prognostic Metastatic Phenotypes

Nicholas Zaorsky, MD, MS, who recently joined the Department of Radiation Oncology at UH Seidman Cancer Center, and colleagues have used “big data” techniques using more than 400,000 patient records in the National Cancer Database to develop five distinct phenotypes of metastatic disease: (Stage IVA) nearly-exclusive bone-only metastases, commonly seen in lung, breast, and prostate cancer; (IVB) predominant lung metastases, commonly seen in breast, stomach, kidney, ovary, uterus, thyroid, cervix, and soft tissue cancer; (IVC) predominant liver/lung metastases, commonly seen in colon, rectum, pancreas, lung, esophagus, and stomach cancer; (IVD) bone/liver/lung metastases predominant over brain, commonly seen in lung and breast cancer; (IVE) brain/lung metastases predominant over bone/liver, commonly seen in lung cancer and melanoma. This novel pan-cancer staging system for metastatic disease, termed STARS, is significantly more prognostic than AJCC staging. Further, it can be used in all communities, since it relies on readily available, inexpensive predictors, is simple and allows for rapid validation.

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