Jennifer Gile, MD, on High-Risk DLBCL: frontMIND and POLARIX Regimens
Thematic Newsreels
Jennifer Gile, MD, of Willamette Valley Cancer Institute, talks about the first positive phase III trials in the high-risk diffuse large B-cell lymphoma (DLBCL) space—POLARIX and frontMIND. POLARIX established the superiority of a modified regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) called pola-R-CHP, in which vincristine was replaced with polatuzumab vedotin, over standard R-CHOP; frontMIND showed that the addition of the CD19 monoclonal antibody tafasitamab plus the immunomodulatory drug lenalidomide to R-CHOP also improved outcomes over standard R-CHOP. Dr. Gile discusses current considerations when choosing between these regimens and how future research may lead to even more refined patient selection.
The ASCO Post Staff
Raajit K. Rampal, MD, PhD, Director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, reviews the four FDA-approved Janus kinase (JAK) inhibitors for patients with myelofibrosis, touching upon differences in their mechanisms of action and toxicity profiles. He also discusses clinical trials of add-on drugs to the currently approved JAK inhibitors, which may increase their efficacy and durability, as well as trials of novel JAK inhibitors and immunotherapies targeting CALR.
The ASCO Post Staff
Kent Shih, MD, of Tennessee Oncology, shares three patient cases that illustrate how gene-expression profiling (GEP) in patients with melanoma helps shape the decision to proceed to sentinel lymph node biopsy (SLNB) and how often and thorough follow-up should be with medical oncology.
Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, discusses research into moving KRAS G12C inhibitors from the second to the first line, as well as combining them with immunotherapies and EGFR antibodies. Some potential combinations under investigation include KRAS G12C inhibitors (such as olomorasib, fulzerasib, divarasib, and adagrasib) and single-agent immunotherapy (pembrolizumab) or EGFR-targeting therapies (cetuximab).
The ASCO Post Staff
Raajit K. Rampal, MD, PhD, Director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses management strategies for these two conditions often associated with myelofibrosis. He discusses the role of Janus kinase inhibitors; using older therapies in novel ways; how stem cell transplantation is considered; and more.
References
- Marrone M, Morere L, Oladapo A, et al: Hematologic improvement experienced by pacritinib-treated patients with myelofibrosis in real-world clinical settings. Blood 144 (suppl 1):3814, 2024.
- Rampal RK, Verstovsek S, Devlin SM, et al: Safety and efficacy of combined ruxolitinib and thalidomide in patients with myelofibrosis: A phase II study. Blood 134 (suppl 1):4163, 2019.
The phase III frontMIND trial demonstrated improved outcomes vs R-CHOP in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), paralleling the POLARIX trial. Despite efficacy, tafasitamab/lenalidomide/R-CHOP has not achieved comparable guideline adoption. Uncertainty regarding overall survival benefit, limited follow-up, cross-trial comparisons, and implementation complexity may contribute to the underutilization of this regimen despite its manageable toxicity.
