Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS)

Abstract

Myelodysplastic syndromes (MDS) treated with DNMTI therapy have responses according to the 2006 IWG response criteria. CR responses have had the strongest association with OS. Recently, CR with partial hematologic recovery (CRh; i.e. blasts <5%, ANC > 500, platelets > 50) has been evaluated in AML, but its relevance is unknown in MDS. We identified adult patients with MDS treated with DNMTIs. We assessed best overall response to therapy according to IWG 2006 criteria, and subsequently identified patients meeting CRh criteria from the subgroup with SD or mCR. We evaluated duration of therapy and overall survival according to response. We identified 311 patients with MDS who received treatment between 2007 and 2018. The median age at the time of therapy was 69 years (range 23-91). Median follow up was 60 months. According to IWG 2006, responses included CR (n = 43, 14%), PR (n = 2, 1%), mCR (n = 57, 18%), SD (n = 149, 48%) and PD (n = 60, 19%). 79 patients (25%) achieved HI. A total of 62 patients (20%) met CRh criteria leading to reclassification of mCR (now n = 26, 8%) or SD (now n = 118, 38%). Patients achieving CR had similar time on therapy (median 8.1mo) compared to CRh (median 6mo, HR 1.4, 95% CI 0.9-2.0), and longer than other responses (p < 0.001). OS varied according to response; median OS was similar between CR (23.3mo) and CRh (25mo, HR 1.28 [0.79-2.08]), which was longer than those with mCR (17.2mo, HR 1.71 [0.96-3.05]), SD (16.3mo, HR 1.61 [1.04-2.48]), and PD (8.7mo, HR 3.04 [1.91-4.83]) (p < 0.001). OS associations with CR/CRh were confirmed in multivariable analysis accounting for allogeneic transplant. MDS patients who achieve a CRh response had similar survival and duration on therapy as patients who achieve CR response and superior to other IWG responses. These data support further evaluation of CRh into future response criteria and clinical trials.

Fig. 1. General classification of responses according to IWG 2006 response criteria (left) and when adding CRh as a response (right).

Patients with marrow complete remission or stable disease were reclassified as CRh if, during therapy, they met the criteria for this metric.

Fig. 2. Overall survival from the time of therapy initial until death or last known alive, among patients treated with DNMTI therapy.

Survival is shown according to the best overall response on DNMTI therapy (IWG 2006 criteria). Patients with CR as the BOR had prolonged survival compared to mCR, SD, and PD (p < 0.001).

Fig. 3. Overall survival from the time of therapy initial until death or last known alive, among patients treated with DNMTI therapy.

Survival is shown according to the best overall response on DNMTI therapy (IWG 2006 criteria) but including patients who met CRh and reclassifying them from patients who met mCR or SD. Median OS was similar between CR (23.3mo) and CRh (25mo). This was longer than patients whose best response remained classified as mCR (17.2mo), SD (16.3mo), and PD (8.7mo) (p < 0.001).