Researchers from The University of Texas MD Anderson Cancer Center are presenting compelling findings from three medical trials on the 2022 American Society of Hematology (ASH) Annual Meeting. These oral shows spotlight encouraging outcomes to advance the usage of focused therapies and novel combos in a number of sorts of leukemia, together with high-risk and newly identified acute myeloid leukemia (AML) in older and youthful sufferers and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). More data on all ASH Annual Meeting content material from MD Anderson will be discovered at MDAnderson.org/ASH.
Older or high-risk sufferers with newly identified AML reply properly to triplet remedy (Abstract 61)
Researchers noticed encouraging response charges in older or high-risk sufferers with newly identified acute myeloid leukemia (AML) who have been handled with the triplet mixture remedy of azacitidine, venetoclax and magrolimab on a Phase Ib/II trial. The newly identified cohort had an 80% total response charge (ORR), and the median total survival (OS) was not but reached at a median follow-up of 9.2 months. Naval Daver, M.D., affiliate professor of Leukemia, introduced research outcomes Dec. 10.
“We are inspired by the promising proof of this triplet remedy as a remedy choice for older or unfit sufferers with AML,” Daver mentioned. “We will proceed to increase the trial to incorporate extra sufferers, and we have now initiated a world Phase III randomized research evaluating the triplet remedy versus the doublet azacitidine-venetoclax. If the research is constructive, it might set up a brand new frontline customary of look after these sufferers.”
About 50-55% of sufferers with AML are thought-about older or unfit for intensive chemotherapy. Frontline remedy with azacitidine and venetoclax achieves response charges of 65-70% in newly identified sufferers, however most sufferers will relapse and people with TP53 mutations proceed to have poor outcomes, with median OS of lower than six months. Magrolimab is an anti-CD47 antibody that works to dam the “do not eat me sign” on leukemia cells. In a earlier trial, it demonstrated efficacy with azacitidine in newly identified AML, with an particularly encouraging sign of response and survival in frontline TP53-mutated AML.
The present trial enrolled 74 sufferers throughout two cohorts. The first cohort enrolled 45 frontline sufferers aged 75 or older with documented comorbidities that made them ineligible for intensive remedy or with adversarial threat elements and/or a TP53 mutation, no matter age. This cohort included 27 sufferers with a TP53 mutation and 14 with out. The second cohort enrolled 29 sufferers with relapsed/refractory (R/R) illness.
All sufferers who obtained no less than one dose of any of the three research medication have been included for response and adversarial occasions. Eighteen sufferers skilled better than grade 3 anemia, and the most typical non-hematologic unintended effects have been febrile neutropenia, pneumonia, hyperbilirubinemia, transaminitis, creatine elevation and hypokalemia.
In the newly identified cohort, the ORR in sufferers with and with out TP53 mutations was 74% and 93%, respectively. Median OS was not but reached for both group of sufferers. Responses in sufferers with R/R illness with prior venetoclax remedy have been modest, and the cohort was closed for futility. Patients with R/R illness with out venetoclax publicity nonetheless are being enrolled.
The research was funded by Gilead. Daver has served in an advisory position for Gilead.
Chemotherapy-free routine ponatinib plus blinatumomab efficient in sufferers with newly identified Ph+ ALL (Abstract 213)
The chemotherapy-free routine of ponatinib and blinatumomab achieved excessive response charges and decreased the necessity for an allogeneic stem cell transplant for sufferers with just lately identified Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), based on outcomes from a Phase II trial. One of the lead investigators, Nicholas Short, M.D., assistant professor of Leukemia, introduced the findings Dec. 10.
“Traditionally, Ph+ ALL responds poorly to plain chemotherapy and is high-risk for relapse, so these survival outcomes and decreased want for a stem cell transplant are very encouraging,” Short mentioned. “Not solely does this routine look like a secure and efficient chemotherapy-free choice, but it surely additionally appears to beat the historic want for transplant in these sufferers.”
Patients with Ph+ ALL have traditionally had poor long-term survival charges. Researchers have discovered including tyrosine kinase inhibitors (TKIs), similar to ponatinib, to chemotherapy can drastically enhance survival. Ponatinib is a third-generation TKI that targets BCR-ABL1 and is historically used to deal with sure sorts of power myeloid leukemia. Blinatumomab is a CD3-CD19 bispecific antibody that’s efficient as a single agent in relapsed or refractory Ph+ ALL.
The trial enrolled 40 sufferers with newly identified Ph+ ALL. Patients with uncontrolled heart problems or clinically vital central nervous system comorbidities have been excluded from the research. The common age of members was 56 years previous.
Of the sufferers that have been evaluable for a hematologic response, 96% had a whole remission or full remission with incomplete rely restoration. Among the 38 sufferers who have been evaluable for full molecular response (CMR), 68% achieved CMR after one remedy cycle and 87% achieved CMR throughout the trial interval. Molecular responses have been speedy, with a majority of sufferers reaching CMR within the peripheral blood inside two weeks of remedy. Only one affected person underwent stem cell transplant in first remission.
At a median follow-up of 15 months, event-free and estimated total survival was 95%. These encouraging outcomes have been noticed regardless of the very low charge of transplant within the research. The remedy was properly tolerated, and most toxicities have been grade 1-2 and in line with recognized unintended effects of the 2 brokers.
The research was funded by Amgen and Takeda Oncology. Short has served in a consulting or advisory position for Takeda Oncology.
Venetoclax with CLIA extremely efficient in youthful sufferers with newly identified AML, high-risk MDS (Abstract 709)
The newest outcomes of a Phase II research evaluating the addition of venetoclax to the intensive chemotherapy remedy of cladribine, idarubicin and cytarabine (CLIA) as a frontline remedy demonstrated excessive charges of illness management and remissions in youthful sufferers with newly identified AML and high-risk myelodysplastic syndrome (MDS). In the research, 96% of sufferers responded to remedy and 90% had no measurable illness detected in a bone marrow pattern. Patrick Reville, M.D., teacher of Leukemia, introduced up to date outcomes and longer-term follow-up knowledge Dec. 12.
“Venetoclax has been a breakthrough for AML sufferers which can be ineligible for intensive remedy. This knowledge continues to reveal the good thing about together with venetoclax with the CLIA induction routine,” Reville mentioned. “This routine is resulting in unprecedented response and measurable residual disease-negativity charges. As we proceed to observe members, we’re inspired by their long-term outcomes and survival.”
The single-center, single-arm trial enrolled 67 sufferers with a median age of 48. Sixty sufferers had AML and 4 sufferers had high-risk MDS. In addition, three sufferers had a mixed-phenotype acute leukemia (MPAL).
The composite full response charge was 96% throughout all sufferers and 100% for sufferers with each MDS and MPAL with a myeloid predominant clone. Most sufferers went on to obtain a subsequent allogeneic stem cell transplant (alloSCT), together with 70% of those that responded to remedy.
Encouragingly, with a median follow-up of simply over two years, the median period of response, event-free survival and total survival haven’t but been reached. At 12 months, the estimated event-free survival charge is 70% and the estimated total survival charge is 86%. Seventy-four % of responding sufferers are estimated to have an ongoing response at 12 months.
The most typical non-hematologic adversarial occasion that members skilled was febrile neutropenia, which was managed. Researchers proceed to observe sufferers and research this remedy routine as a secure and efficient induction remedy technique for this affected person inhabitants.
The research was funded by the Joe Moakley Leukemia SPORE and MD Anderson institutional assist.