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And You Can Tell Everybody This Is Your Song: The Best of #ASH22 — Malignant Hematology

December 18, 2022
Amanda Blackmon, DO, and Idoroenyi Amanam, MD

Dr. Amanda Blackmon (@mlblack1_b) returns this year after serving as a Junior Author in 2021. Originally from Gaithersburg, Maryland, she attended the University of Maryland for undergrad, earned her MS at Georgetown University, and attended medical school at the Philadelphia College of Osteopathic Medicine in Philadelphia. After her residency at Pennsylvania Hospital, Dr. Blackmon headed west for fellowships at University of California Irvine, and City of Hope National Medical Center in Duarte. She is currently an assistant professor of leukemia and hematopoietic cell transplantation at City of Hope, where she focuses on leukemia, myelodysplastic syndromes, and transplantation. She lives in Pasadena, where she is “enjoying the craziness of a dual physician family with a toddler.” Her hobbies, conveniently, mirror those of her 2-year-old: “jumping (why not?), dancing, exploring the world, lots of snacking, nap time.” Dr. Blackmon might also have a fallback career in the works. “If I wasn’t a hematologist, my dream would be to be on Broadway. It’s never too late.” True words.

Dr. Blackmon is joined by her Co-Author Dr. Idoroenyi Amanam, who is also based at City of Hope where he is an assistant professor of leukemia and hematopoietic cell transplantation, focusing on leukemia, stem cell transplantation, and myeloproliferative neoplasms. He is a triple-boarded physician with advanced fellowship training utilizing cellular and stem cell therapy to treat malignant conditions. He completed his hematology and oncology training at City of Hope, serving as chief fellow. He was then awarded the prestigious City of Hope Hematopoietic Cell Transplantation and Cellular Therapy Fellowship, with a concentration on acute leukemias and myeloproliferative neoplasms. Dr. Amanam was awarded a Congressional Award in voluntary public service, and he carries this spirit into the clinic. “I believe in treating all my patients with compassion and utilizing intellectual curiosity to tailor my treatment approaches,” he shared. He also believes he was chosen to enter this field as he had a loved one who struggled with cancer and lived years longer than expected thanks to compassionate care by the doctors and nurses.

Recurrent themes at this year’s ASH annual meeting included molecular characterization of disease, novel targeted therapies such as sequencing of therapies as well as cellular therapies, and measurable residual disease (MRD) assessment. If you’re anything like us and left the meeting feeling motivated but a little overwhelmed, here is the reader’s digest version, outlining a few of the year’s notable abstracts  so you can get back to Elton John’s greatest hits and prepare for next year’s abstract submission.

Acute Lymphoblastic Leukemia (ALL)

As part of the Late-Breaking Abstracts session, the phase III ECOG-ACRIN E1910 study (abstract #LBA-1, presented by Dr. Mark Litzow [pictured left]) demonstrated a survival benefit with the addition of blinatumomab to consolidation chemotherapy in patients with newly diagnosed Philadelphia chromosome negative (Ph-) B-lineage ALL who achieved MRD negative remission after intensification chemotherapy. This study is practice changing, and blinatumomab consolidation therapy will be a new standard of care for adult patients with Ph- B-ALL.

Additionally, several studies on inotuzumab (anti-CD22 monoclonal antibody) were presented this year, particularly in the frontline setting for Ph- B-ALL. Results from the phase II EWALL-INO study (abstract #2724) showed efficacy of frontline fractionated inotuzumab in combination with low-intensity chemotherapy in patients older than 55 years with 20 percent or more blasts expressing CD22 and without central nervous system involvement. Complete remission (CR) rate with or without platelet recovery (CRp) was 90 percent, with MRD less than 10-4 achieved in 80.8 percent after two cycles of induction therapy. Grade 3-4 liver toxicity occurred in 16 percent of patients, 2.2 percent with transient sinusoidal obstruction syndrome. We look forward to learning how many of these patients underwent allogeneic transplantation and about the incidence of veno-occlusive disease (VOD).

A phase II study from University of Texas MD Anderson Cancer Center (abstract #4043) evaluating the addition of inotuzumab to hyper-CVAD (hyperfractioned cyclophosphamide, vincristine, adriamycin, and dexamethasone), plus blinatumomab, in younger patients aged 14 to 59 years with newly diagnosed Ph- B-ALL showed promise for the regimen as safe and effective, with a trend toward an overall survival benefit. The Gimema ALL2418 phase II study of inotzumab in adults with MRD-positive disease before hematopoietic stem cell transplantation (abstract #2726) demonstrated efficacy in obtaining MRD negativity prior to transplant, including in 20 percent of patients who had previously received blinatumomab. Only one of 39 patients had VOD, which occurred prior to transplant. Similarly, a phase II study from MD Anderson (abstract #1411) also showed efficacy of inotuzumab in MRD+ B-ALL, including in those who had prior blinatumomab exposure, with 7 percent incidence of VOD. To follow up on this, VOD risk in patients receiving inotuzumab may be alleviated by fractionation of inotuzumab dose, avoiding concurrent azole antifungals, and routine ursodiol use peri–stem cell transplantation (abstract #1367).

Acute Myeloid Leukemia (AML)

Many new agents are being studied in combination with hypomethylating agents (HMA) +/- venetoclax. The phase II study of azacitidine with venetoclax and magrolimab in older/unfit patients with newly diagnosed and relapsed/refractory (R/R) AML (abstract #61) had similar CR/CRi rates compared to previous reported responses with HMA plus venetoclax. In the R/R setting, those with prior venetoclax exposure had particularly poor responses, which resulted in closure of the study arm. To follow, in an analysis of patients who failed frontline hypomethylating agents with venetoclax (abstract #537), the presence of TP53 and K/NRAS mutations were predictors of inferior survival. The COMMAND study (abstract #599) presented retrospective data showing improved long-term outcomes of allogeneic transplantation in patients with TP53-mutated AML, particularly in those achieving CR at day 100, and with chronic graft-versus-host disease (GVHD).

Venetoclax combinations with intensive regimens are also on the horizon. Phase II data on venetoclax combined with cladribine, idarubicin, and cytarabine in younger/fit patients with AML and high-risk myelodysplastic syndromes (MDS) (abstract #709) showed high rates of MRD-negative remissions in patients with AML regardless of European LeukemiaNet risk group.

In relapsed/refractory AML with KMT2A rearrangement or NPM1 mutations, phase I data on menin inhibition with SNDX-5613 showed activity in patients having received a median of four lines of treatment. The safety profile appeared manageable, with dose-limiting toxicity of asymptomatic QT prolongation (abstract #63). Complete response rate (CR+CRh+CRp) was 38 percent, and of those, 78 percent had MRD- remissions.

Clarifications on MRD significance in AML are also underway. In a retrospective analysis from Germany that included patients with pretransplantation MRD samples (abstract #2129), the presence of NPM1 by quantitative polymerase chain reaction did not affect post-transplant outcomes in patients achieving CR.


Several studies highlighted the use of the international prognostic scoring system molecular risk stratification score (IPSS-M). A single-center retrospective study comparing the IPSS-M to IPSS-R showed higher discriminative potential of IPSS-M in terms of ability to predict AML transformation and all-cause mortality (abstract #1778). Similar studies (abstract #3087 and #4397) described the mutational profile of patients with MDS and their prognostic relevance.

Myeloproliferative Neoplasms (MPN)

The plenary session on INCA033989, a monoclonal antibody (mAb) that selectively antagonizes mutant calreticulin (CALR) oncogenic function in MPN is exciting for the MPN community (abstract #6). This mAb is a high-affinity human IgG1 that selectively binds mutant CALR, abrogating thrombopoietin receptor–induced signaling and subsequent downstream JAK-STAT pathway activation.

In chronic myeloid leukemia and Ph+ ALL, olverembatinib, a novel third-generation BCR-ABL1 tyrosine kinase inhibitor was shown to have activity in heavily pretreated patients, including those with T315I mutation and prior exposure to ponatinib or asciminib (abstract #82).

Hematopoietic Stem Cell Transplantation

The big news this year surrounded BMT CTN 1703 (abstract #LBA-4), which met its primary endpoint showing a higher one-year GVHD/relapse or progression-free survival with post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil compared to tacrolimus/methotrexate, with improvement in GVHD risk without increased risk of relapse or death. This is practice changing and emerges as the standard of care for closely matched, as well as mismatched, transplants.

Non-Hodgkin Lymphoma

The Triangle trial (abstract #1) presented at the plenary session this year demonstrated the addition of ibrutinib to frontline chemoimmunotherapy in younger patients with mantle cell lymphoma may obviate the need for autologous stem cell transplantation. 

Conversely, the international phase III trial (MATRix/IELSG43) in primary central nervous system lymphoma showed an impressive survival benefit with high-dose chemotherapy followed by autologous transplant as compared to consolidation with chemoimmunotherapy (abstract #LBA-3).

Chronic Lymphocytic Leukemia (CLL)

Just when you thought the treatments could not get any better, the final analysis of the phase III ALPINE study (abstract #LBA-6) demonstrated superior progression-free survival and overall response rates with zanubrutinib compared with ibrutinib in patients with R/R CLL/small lymphocytic leukemia in the first head-to-head comparison of Bruton tyrosine kinase inhibitors.

Furthermore, in patients with CLL who develop Richter syndrome, data from a phase Ib/II study on a promising new subcutaneous CD3-CD20 bispecific antibody, epcoritamab, showed impressive single-agent activity, with a manageable safety profile that included low-grade cytokine release syndrome (abstract #348).

Multiple Myeloma (MM)

As the myeloma toolbox has rapidly expanded in the past few years, it is difficult to keep up with the nuances, for instance whether and when to treat smoldering myeloma. Data from the ASCENT trial using fixed duration therapy with daratumumab, carfilzomib, lenalidomide, and dexamethasone for high-risk smoldering multiple myeloma were presented showing high rates of MRD-negative remissions, possibly eliminating the clones that develop into MM (abstract #757).

Cellular therapy for MM has also expanded. Phase I data for frontline use of dual-targeted FasT CAR-T cellular therapy (GC012F) in transplant eligible patients showed 100 percent response rate in the first 13 patients, all of whom were MRD negative (abstract #366).

And last but not least, the MajesTEC 1 correlative study on the U.S. Food and Drug Administration–approved B-cell maturation antigen (BCMA) × CD3 bispecific antibody, teclistamab, for R/R MM described nonresponders as those with unfavorable immune profiles (abstract #97). This unfavorable profile included “lower T-cell numbers, higher proportion of T cells expressing markers such as PD-1, TIM-3, and CD38, higher frequency of Tregs particularly CD38+ Tregs, and lower proportion of naïve T cells with more [natural killer] cells.”

#ASH 2022

The biggest highlight was seeing all of you in person and celebrating life together in New Orleans!  And while it may have been the last Elton John tour, we will always have future ASH annual meetings to look forward to. “I hope you don’t mind, I hope you don’t mind, that I put down in words… how wonderful life is when you’re in the world.”

Dr. Amanam and Dr. Blackmon indicated no relevant conflicts of interest.

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