Focused therapies and novel drug combos present promise for the therapy of a number of leukemias

Researchers from The College of Texas MD Anderson Most cancers Heart are presenting compelling findings from three scientific trials on the 2022 American Society of Hematology (ASH) Annual Assembly. These oral shows spotlight encouraging outcomes to advance using focused therapies and novel combos in a number of sorts of leukemia, together with high-risk and newly recognized acute myeloid leukemia (AML) in older and youthful sufferers and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Extra info on all ASH Annual Assembly content material from MD Anderson could be discovered at MDAnderson.org/ASH.

Older or high-risk sufferers with newly recognized AML reply properly to triplet remedy (Summary 61)

Researchers noticed encouraging response charges in older or high-risk sufferers with newly recognized acute myeloid leukemia (AML) who have been handled with the triplet mixture remedy of azacitidine, venetoclax and magrolimab on a Section Ib/II trial. The newly recognized cohort had an 80% total response price (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, offered research outcomes Dec. 10.

“We’re inspired by the promising proof of this triplet remedy as a therapy choice for older or unfit sufferers with AML,” Daver mentioned. “We are going to proceed to increase the trial to incorporate extra sufferers, and we’ve got initiated a world Section 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 commonplace of take care of these sufferers.”

About 50-55% of sufferers with AML are thought-about older or unfit for intensive chemotherapy. Frontline therapy with azacitidine and venetoclax achieves response charges of 65-70% in newly recognized 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 recognized 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 primary 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 at the least one dose of any of the three research medicine have been included for response and adversarial occasions. Eighteen sufferers skilled higher than grade 3 anemia, and the commonest non-hematologic uncomfortable side effects have been febrile neutropenia, pneumonia, hyperbilirubinemia, transaminitis, creatine elevation and hypokalemia.

Within the newly recognized 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 therapy have been modest, and the cohort was closed for futility. Sufferers 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 recognized Ph+ ALL (Summary 213)

The chemotherapy-free routine of ponatinib and blinatumomab achieved excessive response charges and diminished the necessity for an allogeneic stem cell transplant for sufferers with lately recognized Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), in keeping with outcomes from a Section II trial. One of many lead investigators, Nicholas Quick, M.D., assistant professor of Leukemia, offered the findings Dec. 10.

“Historically, Ph+ ALL responds poorly to straightforward chemotherapy and is high-risk for relapse, so these survival outcomes and diminished want for a stem cell transplant are very encouraging,” Quick mentioned. “Not solely does this routine look like a secure and efficient chemotherapy-free choice, however it additionally appears to beat the historic want for transplant in these sufferers.”

Sufferers with Ph+ ALL have traditionally had poor long-term survival charges. Researchers have discovered including tyrosine kinase inhibitors (TKIs), corresponding 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 continual 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 recognized Ph+ ALL. Sufferers with uncontrolled heart problems or clinically vital central nervous system comorbidities have been excluded from the research. The common age of individuals was 56 years outdated.

Of the sufferers that have been evaluable for a hematologic response, 96% had an entire remission or full remission with incomplete rely restoration. Among the many 38 sufferers who have been evaluable for full molecular response (CMR), 68% achieved CMR after one therapy cycle and 87% achieved CMR throughout the trial interval. Molecular responses have been fast, with a majority of sufferers reaching CMR within the peripheral blood inside two weeks of remedy. Just 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 price of transplant within the research. The therapy was properly tolerated, and most toxicities have been grade 1-2 and per recognized uncomfortable side effects of the 2 brokers.

The research was funded by Amgen and Takeda Oncology. Quick has served in a consulting or advisory position for Takeda Oncology.

Venetoclax with CLIA extremely efficient in youthful sufferers with newly recognized AML, high-risk MDS (Summary 709)

The newest outcomes of a Section II research evaluating the addition of venetoclax to the intensive chemotherapy therapy of cladribine, idarubicin and cytarabine (CLIA) as a frontline remedy demonstrated excessive charges of illness management and remissions in youthful sufferers with newly recognized AML and high-risk myelodysplastic syndrome (MDS). Within the research, 96% of sufferers responded to therapy and 90% had no measurable illness detected in a bone marrow pattern. Patrick Reville, M.D., teacher of Leukemia, offered up to date outcomes and longer-term follow-up information Dec. 12.

“Venetoclax has been a breakthrough for AML sufferers which are ineligible for intensive remedy. This information continues to exhibit 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 individuals, we’re inspired by their long-term outcomes and survival.”

The one-center, single-arm trial enrolled 67 sufferers with a median age of 48. Sixty sufferers had AML and 4 sufferers had high-risk MDS. As well as, three sufferers had a mixed-phenotype acute leukemia (MPAL).

The composite full response price 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 therapy.

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 price is 70% and the estimated total survival price is 86%. Seventy-four p.c of responding sufferers are estimated to have an ongoing response at 12 months.

The most typical non-hematologic adversarial occasion that individuals skilled was febrile neutropenia, which was managed. Researchers proceed to observe sufferers and research this therapy routine as a secure and efficient induction therapy technique for this affected person inhabitants.