Talha Badar: Moving immunotherapy upfront in B-cell ALL
Moving immunotherapy upfront in B-cell ALL.
Due to increased understanding of disease biology, resistance/toxicity from chemotherapy, field is moving towards early introduction of targeted molecule and immunotherapy.
INO, an anti-CD22 Ab was approved for RR ALL based on INO-VATE study:
- higher CR rate 81% vs 29%; P < .001); MRD 78% vs 28% after SOC P < .001.
Among the patients who received allo-HSCT after INO, 22% had VOD
DOI: 10.1056/NEJMoa1509277
Phase II study of InO plus mini hyper CVD upfront for B-cell ALL; 2 yrs PFS was 59% and OS 66%.
Click here for the article.
Several trials now incorporating InO ealry in Rx of B-cell ALL below.
Blinatumomab (CD3-CD19 bispecific) was approved for RR B-cell ALL based on positive results of PIII:
- higher ORR 44% vs. 25%, P<0.001
- mOS 7.7 vs 4.0 mo.
DOI: 10.1056/NEJMoa1609783
HyperCVAD plus sequential Blina for Ph-ve B-cell ALL.
4 # of HyperCVAD leads to 4 # of Blina leads to 3 cycles of POMP alternating with 1 cycle of Blina for 15 cycles.
- 38 pts: CR 100%,
- MRD -ve 97%, 3-yr OS 81%
Impressive results, including pts with HR disease.
10.1016/S2352-3026(22)00285-X
Blina followed by POMP maintenance in elderly with Ph-ve B cell ALL (SWOG 1318).
29 pts, median age 75 yrs, poor risk 34%.
CR 66%, 3 yrs DFS and OS 37% each
DOI: 10.1200/JCO.21.01766
E1910 trial incorporating Blina with chemotherapy in MRD -ve B-cell ALL.
Primary endpoint was OS and it was met!
Chemotherapy free Rx for elderly B-cell ALL: InO and Blina for older:
Alliance A041703
Phase II trial of induction InO then blina for older adults with newly-diagnosed (ND), Ph-, B-ALL.
- 33 pts, CR after course II 97%, 1 yr EFS 75%, 1 yr OS 84%.
Click here for the article.
Several trials now incorporating Blina early in Rx of B-cell ALL below.
Chemo-free regimen for Ph+ve ALL with upfront immunotherapy.
Excellent responses with 2 yrs OS > 90%.
Click here for the article.
Summary:
It is high time to incorporate immunotherapy upfront in Rx of B-cell ALL:
- Less toxic
- More effective with durable responses
- Effective in high risk pts. “
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