Lancet Haematol: Panatinib in combination with bonatumab for Ph-positive acute lymphoblastic leukemia

Ponatinib (panatinib) and blinatumomab (bonatumab) are effective treatments for patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia, and their combined regimens may be a promising treatment option
.
In the study, the researchers evaluated the efficacy and safety
of this combination regimen without chemotherapy in patients with Ph-positive acute lymphoblastic leukemia.

This is a single-center, single-arm Phase 2 clinical trial enrolling patients aged 18 years of age with newly diagnosed or relapsed/refractory Ph-positive acute lymphoblastic leukemia or chronic myeloid leukemia, and requires ECOG performance status ≤ 2 points, total bilirubin not exceeding twice the upper limit of normal (≤ 2.
4 mg/dL), and aminotransferase, serum lipase, and amylase concentrations not exceeding 3 times
the upper limit of normal.
Panatinib 30mg orally, bonatumab 28ug intravenous drip, 28 days as a course of treatment, after 5 courses of change to panatinib monotherapy maintenance
.
The primary endpoints were molecularly complete response rate in newly diagnosed patients and overall response rate
in relapsed/refractory patients.

From 6 February 2018 to 6 May 2022, a total of 72 patients were evaluated, of whom 60 were treated with panatinib and bonatumab (40 newly confirmed Ph-positive acute lymphoblastic leukemia, 14 patients with relapsed/refractory Ph-positive acute lymphoblastic leukemia, and 6 patients with chronic myeloid leukemia).

The median follow-up was 16 months
.
Of the newly diagnosed pH-positive acute lymphoblastic leukemia patients, 33 of the 38 evaluable patients achieved complete molecular responses
.
Thirteen evaluable patients with relapsed/refractory Ph-positive acute lymphoblastic leukemia achieved an overall response and 11 (79%) achieved a complete molecular response
.
Five of the six patients with chronic myeloid leukemia achieved an overall response, including two (33%) complete molecular responses
.

The most common grade 3 to 4 adverse reactions (incidence >5%) were infection (37%), elevated amylase or lipase (8%), elevated aminotransferases (7%), pain (7%), and hypertension (7%)
.
One patient discontinued bonatumab
for tremor.
Three patients discontinued panatinib
due to secondary cerebral ischemia, portal vein thrombosis, and coronary artery stenosis (one case each).
No treatment-related deaths
.

In summary, the combination of panatinib and bonatumab without chemotherapy produced a high rate of complete molecular response in newly diagnosed or relapsed/refractory Ph-positive acute lymphoblastic leukemia patients, which avoided chemotherapy-related toxicity
.

Original source:

Elias Jabbour, et al.
Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial.
The Lancet Haematology.
November 16, 2022.
https://doi.
org/10.
1016/S2352-3026(22)00319-2