Talha Badar: Upfront immunotherapy with or without chemotherapy for precursor B-cell ALL

Talha Badar, Hematologist/Oncologist at Mayo Clinic Comprehensive Cancer Center, posted on X/Twitter:

“Upfront immunotherapy +/- chemotherapy for precursor B-cell (BCP) ALL.

From Rituximab to Inotuzumab (InO) to Blinatumomab to InO/Blina to “chemo free” induction.

Review of literature in this thread:

1. Initially, Rituximab was evaluated with chemo to improve outcome. Based on data suggesting inferior outcome with CD20 + BCP-ALL.
PII study on 31 pt Rx R-hyperCVAD, CR 86%, 3 years EFS 88%, OS 80%. Outcome was better with historical HyperCVAD.

2. PIII trial: R vs no-R with GRAAL Intensive chemo. CR 92% (MRD 65%), 2 year EFS 65% &OS 71% favoring R arm.
However rituximab induction/consolidation is not ideal in elderly with morbidity association with infection, CVD and neurological complications.

3. Inotuzumab showed higher efficacy to chemo in RR BCP-ALL: tested in elderly with mod HyperCVD:

CR 85%, MRD 78%, 3 year PFS/OS 49%/56%.
23% died in CR.
G3-4 liver toxicity in 33%, 8% VOD.

Further modifications in InO required less toxicity.

4. After amendments, Blinatomumab sequentially added to InO+HyperCVD, cumulative dose of InO capped at 2.7 mg/m2 in C1.
With sequential blina, PFS improved from 34.7 to 56.4 mo.

5. GMALL gp conducted a PII trial exploring InO+dex induction followed by age adapted chemo in elderly ALL:
43 pts, 100% CR (71% MRD -ve), 3 yr EFS and OS 55% and 73%.

6. Sequential Blina with HyperCVAD: 4 cycle of chemo > Blina 4 cycles during POMP maintenance:
38 pts, CR 81% (MRD 76%), 3 yrs EFS & OS 73%/81%.

7. PII sequential Blina interspersed with AYA chemo (GIMEMA LAL 2317):
149 pts, CR 88%, MRD 70%: 3 year DFS 65%/ OS 71%.
More MRD – after Blina, Ph like associated with poorer outcome. Similarly, PIII ongoing evaluating InO with 10403 protocol in AYA.

8. E1910 PIII conducted to explore benefit of Blina Consolidation. OS favored Blina: 83% at 3.6 years.
Significant % couldn’t receive Blina due to failure in achieving CR or death.

9. ALLIANCE conducting a PII study of chemo free induction with InO > Blina in Ph-ve BCP-ALL.
31 patients Rx, CR 85% after InO, 97% after Blina. 1 year EFS 75%, OS 84%.

10. Long-term fluorouracil of D-ALBA study: dasatinib + steroids > Blina. 53 months fu estimated EFS and OS: 74% and 80.7%.
IKZF1 plus abn and emergence of T3151 clone association poorer outcome.

11. Blina+ponatinib for Ph+ve ALL: CR 95%, CMR 87%. 2 year EFS and OS 93%. ECOG-ACRIN is conducting PIII study; blina+TKI and TKI+HyperCVAD chemotherapy in treatment naïve Ph+ve ALL patients.

Summary:

B-cell ALL induction regimens are rapidly evolving with utilization of InO and Blina.
LT OS in adults Ph-ve improving from 30-40% to 70-80% with upfront immunotherapy.
Similar improvement in Ph+ve with potent TKI combo LT OS 70-80%; limiting the benefit of allo-HC.”

Source: Talha Badar/X