MD Anderson Research Highlights: ASH 2021 Special Edition

Key presentations focused on therapeutic advances for hematologic cancers

ATLANTA ― The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into basic, translational and clinical cancer research from MD Anderson experts. This special edition features presentations at the 2021 American Society of Hematology (ASH) Annual Meeting on innovative targeted therapies, new combination approaches, and novel cellular therapies to improve treatments for patients with leukemia, lymphoma and other hematologic cancers.

In addition to the studies below, forthcoming press releases will feature groundbreaking clinical studies on chimeric antigen receptor (CAR) T cell therapies for patients with lymphoma (Abstracts 2, 93, 739) and targeted therapies for patients with acute myeloid leukemia (Abstracts 371, 691, 794). Complete information on all ASH Annual Meeting content from MD Anderson can be found at

Sub-analysis of frontline tagraxofusp for blastic plasmacytoid dendritic cell neoplasm (Abstract 874)

Tagraxofusp-erzs, an anti-CD123 targeted therapy, is the first and only approved targeted therapy for treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, but highly aggressive hematologic malignancy. Naveen Pemmaraju, M.D., led the practice-changing Phase I/II clinical trial that showed high response rates in first-line treated patients: complete response (CR) or clinical response (CRc) in 57% of patients and an overall response rate (ORR) of 75%.

A new subgroup analysis reports results from the original clinical trial (across 4 stages) stratified by age and baseline disease involvement (skin only, systemic only, skin and systemic) in the 65 patients who received tagraxofusp as the first line of therapy for BPDCN. Response rates remained high across all cohorts, including older patients and those with extensive baseline disease. In patients age 75 or older, the CR/CRc rate was 55% and ORR was 82%, comparable to patients younger than 60 (CR/CRc 59%, ORR 77%). Patients with both skin and systemic baseline disease had a 50% CR/CRc rate and a 76% ORR. More than half of the patients achieving CR/CRc (median age 63 years) went on to receive hematopoietic stem cell transplantation. Pemmaraju will present the updated subgroup analysis on Dec. 13.

Targeting menin shows early promise for acute leukemias with MLL rearrangements or NPM1 mutations (Abstract 699)

MLL gene rearrangements (MLLr) work with the protein menin to drive expression of leukemia-promoting genes. Leukemias with MLLr occur in infants, children and adults, and are associated with resistance to standard therapies. Similarly, in leukemias with NPM1 mutations (NPM1m) — the most common genetic mutation in acute myeloid leukemia (AML) — menin and MLL interact to drive abnormal gene expression. Preclinical studies have suggested that targeting the interaction between menin and MLL may be an effective strategy for treating MLLr and NPM1m leukemias.

The first-in-human Phase I/II AUGMENT 101 study, led by Ghayas Issa, M.D., evaluated the safety and anti-tumor activity of SNDX-5613 — an oral small-molecule inhibitor of the menin-MLL interaction — for children and adults with advanced MLLr and NPM1m acute myeloid or lymphoid leukemias. SNDX-5613 had an acceptable safety profile, with 18.5% of patients experiencing at least one side effect of grade 3 or higher; no patients discontinued therapy because of treatment-related side effects. In 45 patients with MLLr or NPM1m leukemias, the composite complete remission rate was 44%. Of those patients, 70% had no evidence of minimal residual disease. Early data suggest that SNDX-5613 may be an effective and novel oral targeted therapy for patients with an acute leukemia caused by these genetic alterations. Complete data on the Phase I component of the trial will be presented on Dec. 13.

Drug combination demonstrates superior efficacy in treating DLBCL (Abstract LBA-1)

For two decades, standard-of-care therapy for newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) has been the combination of the antibody rituximab plus chemotherapy drugs cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). However, approximately 40% of patients relapse after initial treatment, so developing a first treatment with a long-lasting response remains an area of clinical unmet need.

In the double-blind, Phase III POLARIX study, R-CHOP was compared with pola-R-CHP, a combination of polatuzumab vedotin — a CD79b-targeting antibody-drug conjugate — and rituximab plus cyclophosphamide, doxorubicin and prednisone (R-CHP). Christopher Flowers, M.D. was the North America leader working with an international team of researchers who enrolled and randomized 879 patients with previously untreated DLBCL. The study demonstrated that pola-R-CHP was more effective than R-CHOP, achieving clinically meaningful improvements in progression-free survival (PFS) with a similar safety profile. The two-year PFS of patients treated with pola-R-CHP was 76.7%, while patients treated with R-CHOP was 70.2%. Overall, pola-R-CHP demonstrated a 27% reduction in the relative risk of disease progression, relapse or death compared with R-CHOP, providing a potential new treatment option for patients with DLBCL. Results of the study will be presented on Dec. 14.

Induced pluripotent stem cell-derived CAR NK therapy shows early promise (Abstract 823)

While current cellular therapies are manufactured from either patient- or donor-derived immune cells, induced pluripotent stem cells (iPSCs) may provide a renewable source of immune cells. FT-596 is an iPSC-derived CAR natural killer (NK) cell therapy targeting CD19+ leukemia and lymphoma cells. Compared with T cell therapies, NK cell therapies are less likely to cause serious toxicities, such as cytokine release syndrome (CRS) or neurotoxicity. Paolo Strati, M.D., led the Phase I dose-escalation study to evaluate FT-596 for patients with relapsed/refractory B-cell lymphomas (BCLs) and chronic lymphocytic leukemia (CLL), either alone or in combination with targeted therapy.

To date, 20 patients with BCL have been treated at escalating dose levels and 17 were evaluated for efficacy. No dose-limiting toxicities were reported, and no patients experienced graft-versus-host disease or neurotoxicities. Two cases of low-grade CRS were reported, but the most common side effects were decreased blood counts, nausea, anemia and fatigue related to lymphodepleting chemotherapy given before FT-596 infusion. Nine patients (53%) achieved an objective response after the first treatment cycle. Of 11 patients receiving more than 90 million cells, seven (64%) achieved a complete response, including 50% of those previously treated with CAR T cell therapy. The data suggest the therapy was well tolerated and demonstrated activity both alone and as part of a combination approach. Updated results from the trial will be presented on Dec. 13.

Researchers offer promising therapy for patients with myeloid/lymphoid neoplasms (Abstract 385)

Complete responses to treatment options for myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement (MLNFGFR1) are rare, with patients often achieving only partial or short-lived complete responses and short life expectancy. Because of the poor prognosis, senior author Srdan Verstovsek, M.D., Ph.D., and researchers tested the safety and efficacy of pemigatinib, a highly selective and potent FGFR1-3 inhibitor, as a treatment option to eliminate the disease and bridge patients to bone marrow transplantation. 

Results from the Phase II, multicenter FIGHT-203 trial showed that pemigatinib is the first therapy to achieve durable and high rates of complete response (CR) and complete cytogenetic responses (CCyR) in patients with MLNFGFR1, providing a promising treatment for those whose disease was resistant to prior therapies, such as intensive chemotherapy and bone marrow transplantation. The study enrolled and treated 34 patients with a daily dose of pemigatinib. Among evaluable patients, the drug achieved CR, CyR and CCyR rates of 64.5%, 72.7% and 75.8%, respectively. While further studies are needed, the results suggest that pemigatinib may offer a long-term treatment option for MLNFGFR1 patients who are ineligible for bone marrow transplantation or may help facilitate bridging eligible patients to bone marrow transplantation. Study results will be presented on Dec. 12.