358P - PPAR GAMMA Agonist in combination with BCR/ABL TKI in patients of CML-CP with suboptimal molecular response

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Leukaemia
Presenter Hemant Malhotra
Citation Annals of Oncology (2016) 27 (suppl_9): ix104-ix111. 10.1093/annonc/mdw586
Authors H. Malhotra1, B. Malhotra2, A. Yadav3, A. Mathur3, D. Biswas2
  • 1Medicine & Medical Oncology, SMS (Sawai Man Singh) Medical College & attached Hospital, 302004 - Jaipur/IN
  • 2Microbiology, SMS (Sawai Man Singh) Medical College & attached Hospital, 302004 - Jaipur/IN
  • 3Medicine, SMS (Sawai Man Singh) Medical College & attached Hospital, 302004 - Jaipur/IN

Abstract

Background

Approximately 10 to 20 % of patients of CML in chronic phase (CML CP) have suboptimal molecular response (MR) to first line Imatinib maleate (IM) treatment. Failure to achieve a complete MR results from the inability of TKIs to eradicate quiescent CML leukaemia stem cells (LSCs). Treatment options for these patients include increasing the dose of IM or switch to a second generation TKI (Nilotinib or Dasatinib). Recently, the addition of PPAR gamma agonists (glitazones) toTKIs has been shown to be toxic to the CML stem cells and the combination to products stem cell depletion. In the present study we report our initial results on 12 patients of CML CP in complete hematological response (CHR) who showed suboptimal molecular response to IM/2nd gen. TKI (as per ELN criteria) and were treated with the combination of TKI plus pioglitazone.

Methods

Twelve patients of CML-CP in CHR but not in major MR (BCR/ABL ABL IS ratio between 1% to 10%) were included in the study. All patients were given Tab. Pioglitazone 30 mg. OD. PO in addition to the TKI. CBC, biochemistry was done every month and BCR/ABL levels on international scale (IS) were estimated every 3 monthly.

Results

Eight patients were on Imatinib maleate (IM) 600 mg OD while 4 patients were on Nilotinib 400 mg. BD. After a mediam follow up of 6 months, 11 of the 12 patients showed a more than 50% decrease in the BCR/ABL ABL ratio, 4 out of the 12 showed a more tha one log decrease and 2 patients had undetectable levels of BCR ABL at the end of 6 months. The combination was well tolerated with only one patient having transient grade I transaminitis which resolved without drug dose decrease or stoppage.

Conclusions

Our priliminary results of this small pilot study indicate that the combination of PPAR gamma agonist, pioglitazone, with a BCR ABL TKI is effective in reducing BCR ABL transcript levels in patients of CML-CP who have not acheived a CMR. The combination is associated with minimal toxicity. Further, larger studies are needed to confirm these findings.

Clinical trial indentification

Legal entity responsible for the study

RK Birla Cancer Center, SMS Medical College & Hospital, Jaipur, India

Funding

Cancer Education & Research Trust

Disclosure

All authors have declared no conflicts of interest.