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.

An agenda to advance research in myelodysplastic syndromes: a TOP 10 priority list from the first international workshop in MDS

“… 23 There is a need to develop and validate new response criteria for higher-risk MDS that capture meaningful clinical benefits, similar to the introduction of CR with partial hematological recovery in ELN 2022 AML criteria. 22 , 24 , 25 Conversely, the elimination of responses with doubtful clinical benefits (eg, marrow CR without meaningful count recovery) should be considered. 26 …”

Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms

“…61 Although CRh has not been shown in MDS to correlate with OS or other hard endpoints, a less stringent PB count recovery in the setting of CR may have meaningful implications for patients with MDS. In HR-MDS, Brunner et al 66 explored CRh as a potential endpoint in MDS and concluded that patients who reached CRh or an equivalent response following treatment had a comparable survival to those who achieved CR. Given the relevance of hematologic recovery in MDS, it is essential to evaluate CRh and CR L and their correlation with OS and therapeutic efficacy in prospective randomized studies.…”

Are We Ready For “Triplet” Therapy in Higher-Risk MDS?

“…49,50 Other meaningful endpoints include the duration of a given response to therapy, as well as overall survival, although these are later endpoints for clinical study. 48 There are additional efforts underway to identify novel responses that are clinically meaningful and may serve as surrogates for overall survival, such as CRh (complete remission with incomplete hematologic recovery) or other combination endpoints, 51 but these remain exploratory at Are We Ready For "Triplet" Therapy in Higher-Risk MDS? this time.…”