Blood Podcast: Review Series on Acute Lymphoblastic Leukemia (ALL)

American Society of Hematology
Episode Airdate: September 18, 2025
Host/Moderator: Dr. Herve Dombre (Associate Editor, Blood; Professor of Rheumatology, Institut de Leukémie, Hôpital Saint-Louis, Paris)
Guest: Dr. Mark Litso (Professor of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN)

Episode Overview

This episode of the Blood Podcast features a focused discussion on a new review series in Blood covering critical developments in acute lymphoblastic leukemia (ALL), with a spotlight on adult B cell precursor ALL. The conversation centers on the evolution of genetic subtyping, the shift toward immunotherapy—including blinatumomab and inotuzumab ozogamicin—frontline treatments, and future trends like CAR T-cell therapy and novel combinations, especially in the context of Philadelphia chromosome-positive ALL.

Key Discussion Points & Insights

1. Structure of the Review Series

[00:39] Dr. Dombre outlines the four-article review series:

• Two reviews detail genetic classification for B cell precursor ALL and T-lineage ALL in adults, which now inform not only diagnosis and risk stratification, but also guide therapeutic decisions.
• A clinical review on the integration of immunotherapy (blinatumomab and others) into frontline regimens for adult B cell precursor ALL.
• An article examining the current and future role of CAR T-cell therapy.

Quote:
"All these new findings in terms of genetic classification are now used not only to classify but also to guide the treatment of those patients with ALL."
— Dr. Dombre [00:39]

2. Incorporation of Immunotherapy: Blinatumomab and Inotuzumab

[02:14] Dr. Litso provides an in-depth overview of immunotherapies entering the frontline:

• Blinatumomab: A bispecific T-cell engager (BiTE) with significant data (including the E1910 and MD Anderson regimens) supporting its use post-induction, leading to improved MRD negativity rates and survival.
• Inotuzumab Ozogamicin: Shows promise both in induction and in chemo-free regimens for older adults, as highlighted by US Alliance Cooperative Group trials.
• Rituximab: Early evidence from the GRAAL trial (French group) shows added benefit when combined with chemotherapy in CD20+ disease.
• CAR T-cell therapy: Touched on as a promising, though still investigational, frontline approach.

Notable Study Results:

• MD Anderson’s HYPERCVAD + blinatumomab regimen allows fewer chemotherapy cycles, high complete remission, and MRD negativity.
• LAL2317 Italian phase II trial: Blinatumomab + chemotherapy increases MRD negativity up to 90%.
• E1910 (US): Blinatumomab in consolidation yielded 85% 3-year OS vs. 68% with chemo alone in MRD-negative patients aged 30–70 (new FDA indication).

Quote:
"Blinatumomab has been studied extensively now in the frontline setting and shown very encouraging results... very high complete remission and MRD negative rates with this regimen in the phase two setting."
— Dr. Litso [02:54]

Chemotherapy-Free Approaches:

• In elderly (>65), inotuzumab followed by blinatumomab (with only intrathecal chemo) resulted in >90% CR, ~80% 1-year survival.

Quote:
"That bodes well for the potential for us to begin to significantly limit the amount of chemotherapy that particularly older patients need to receive."
— Dr. Litso [04:58]

3. About the Optimal Number of Blinatumomab Cycles

[05:38] Dr. Dombre queries ideal cycle number for frontline treatment, noting previous approvals for MRD and relapsed/refractory settings.

[06:38] Dr. Litso responds:

• No definitive answer; trials have varied (Children’s Oncology Group: 2 cycles, E1910: up to 4 cycles).

Quote:
"Our data is with four cycles and so that's what I would recommend... It's conceivable that two cycles might be sufficient."
— Dr. Litso [07:14]

• Maintenance and minimization strategies are ongoing, including adding blinatumomab in maintenance to reduce chemotherapy exposure.

4. Sequential Use of Inotuzumab and Blinatumomab (Debulking and MRD Eradication)

[07:51] Dr. Dombre probes “debulking” with inotuzumab followed by blinatumomab, referencing emerging trial strategies.

[08:21] Dr. Litso explains:

• Blinatumomab is less effective in high blast count settings; optimal in low MRD.
• Inotuzumab does not have this limitation—making it more suited for debulking, followed by blinatumomab for MRD eradication.
• Multiple studies (Alliance, MD Anderson, GMALL, EU-wide) are evaluating this sequencing.

Quote:
"A number of studies are focusing on giving inotuzumab for debulking...and then bringing in blinatumomab...to treat residual disease."
— Dr. Litso [09:04]

5. Philadelphia Chromosome-Positive (Ph+) ALL: TKI-Immunotherapy Combinations

[10:08] Dr. Litso highlights:

• Tyrosine kinase inhibitors (TKIs) revolutionized Ph+ disease by improving outcomes when combined with chemo.
• New studies (Italian, MD Anderson, US) are comparing TKI+blinatumomab vs. TKI+chemo, potentially reducing/eliminating chemotherapy.
  • Ongoing randomized US trial: ponatinib/dasatinib + HYPERCVAD vs. ponatinib/dasatinib + blinatumomab.

Quote:
"Now we have studies that are combining tyrosine kinase inhibitors, particularly ponatinib with blinatumomab and also seeing very excellent outcomes."
— Dr. Litso [10:23]

Notable Quotes & Memorable Moments

• “I think inotuzumab is probably more ideal for debulking and giving it early and then bringing in blinatumomab later is likely the way the field is moving.”
  — Dr. Litso [09:54]
• “There's definitely the potential to reduce the amount of chemotherapy we give...”
  — Dr. Litso [05:23]
• “The optimal treatment [for Ph+ ALL] is not yet determined and all the studies you mentioned are very important to help us to design the optimal treatment with these new agents.”
  — Dr. Dombre [11:28]

Key Timestamps

• 00:39: Review series overview (genetic classification, immunotherapy, CAR T-cell therapy)
• 02:14: Immunotherapy: Blinatumomab and inotuzumab in the frontline; pivotal study discussion
• 05:38: Optimal number of blinatumomab cycles debate
• 07:51: Sequential therapy approaches—using inotuzumab for debulking, blinatumomab for MRD
• 10:08: Ph+ ALL: TKIs and immunotherapy—ongoing research and future paradigms

Conclusions & Recommendations

The field of adult B cell precursor ALL is rapidly evolving, with genetic profiling closely linked to clinical management and immunotherapy reshaping frontline and consolidation strategies. Major takeaways:

• Blinatumomab and inotuzumab are improving outcomes, sometimes allowing significant reduction or even elimination of chemotherapy for select patient populations.
• The optimal sequencing and number of immunotherapy cycles remain under research.
• Integration of immunotherapy in Ph+ ALL, especially in TKI-based regimens, is poised to further improve results.
• Ongoing trials will better define best practices for combining and sequencing these agents.

Final Recommendation:
"I can strongly recommend the readers and the audience to go to your review and read the article if they want more detailed data on this very important topic."
— Dr. Dombre [11:45]