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. “