The edition · Oncology
Chemotherapy-free ponatinib and blinatumomab beat imatinib-chemotherapy in adult Ph-positive ALL
An Italian phase 3 trial in Philadelphia-positive leukaemia, a new prognostic index for metastatic kidney cancer, a pooled look at pneumonitis prediction models, a diet and exercise trial in men on active surveillance, and an FDA supplement entry for pirtobrutinib.
The edition in brief
The GIMEMA ALL2820 phase 3 trial randomised 236 adults with Philadelphia-positive acute lymphoblastic leukaemia 2:1 to ponatinib plus blinatumomab or imatinib plus chemotherapy as frontline treatment. At a median follow-up of 23.7 months, 24-month event-free survival was 86% vs 67% (P < 0.001), survival with no measurable residual disease 68% vs 42%, complete haematological response 94% vs 79%, and cumulative relapse incidence 5% vs 13%. Overall survival was 90% vs 85%. Only 19% of the intervention group had transplantation in first response. A new prognostic model for metastatic clear cell renal cell carcinoma (CPI2), built from CheckMate-214 and validated on CheckMate-9ER (1,747 patients), had discrimination of 0.72 against 0.65 and 0.61 for the IMDC model. A meta-analysis of 12 models predicting checkpoint inhibitor pneumonitis in lung cancer found a pooled validation C-statistic of 0.82 but a prediction interval of 0.51 to 0.95, with only two externally validated, and concluded they are not ready for clinical use. A secondary analysis of a trial in 100 men on active surveillance found a diet and exercise programme produced 7.1% weight loss but no overall quality-of-life gain. The FDA lists a supplement action for pirtobrutinib dated 2 October 2026 without stating the change.
A new prognostic index outperformed the IMDC model in metastatic kidney cancer in the checkpoint inhibitor era
Be aware of the CPI2 index, but continue to use IMDC risk groups in routine care until it is validated outside trials.
FDA lists a supplement action for pirtobrutinib
No change in practice follows from this entry; read the current label if you prescribe pirtobrutinib.
Models to predict checkpoint inhibitor pneumonitis were not ready for clinical use
Do not use machine-learning risk scores to guide immunotherapy decisions yet; keep monitoring for new cough or breathlessness.
Diet and exercise led to weight loss in men on prostate active surveillance without overall quality-of-life gain
Offer weight management to men on active surveillance for general health, without promising better urinary, sexual or cancer-related quality of life.
New breathlessness or cough on a checkpoint inhibitor may be pneumonitis
Treat new respiratory symptoms on immunotherapy as possible pneumonitis until proven otherwise, and involve oncology early.
Ponatinib and blinatumomab without chemotherapy beat imatinib plus chemotherapy in Ph-positive ALL
This chemotherapy-free regimen is a strong candidate for frontline treatment of adult Ph-positive ALL at specialist centres, pending longer follow-up and safety data.
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