UPDATE AND FOLLOW-UP OF NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM) WITH HIGH-RISK CYTOGENETIC (HRC)

ABSTRACT

Background: Despite therapeutic strategies improvement, there is still a subgroup of NDMM patients (pts) that pose a clinical challenge, whose represents a <20%, we refer to HRC. HRC Pts are associated with a poor prognosis and aggressive course, although, recent studies propose different clinical evolution according to the cytogenetic alteration (CA). IMWG identified a 4-year progression free survival (PFS) of 12% and OS of 35%. Aims: Describe our clinical experience and therapeutic management, also the clinical-biochemical alterations at diagnosis in a heterogeneous NDMM HRC's cohort. Evaluate survival curves according to HRC. Methods: Descriptive and retrospective analysis, using clinical and analytical NDMM HRC patient's data from 2009 to 2022 at Guadalajara University Hospital. 61/201 pts were selected in the MM treatment (tto) protocols. FISH results were not found in <30% NDMM, due to lack of metaphases or no request. Pts with t(4;14), t(14;16), gain 1q, t(14;20), plasmablastic leukemia and/or del(17p13) were classified as HRC. Survival data and Pearson (P) correlation were used. P value <0.05 was considered significant. Results: Total HRC NDMM 61 pts were analyzed. 21 of 61 pts (35%) were diagnosed with stage monoclonal gammopathy of undetermined significance (MGUS) prior to HRC NDMM, with a mean 4 years (y) (IR 2-10 y), greater % representation of MGUS were del17p (38), gain 1q (48), t (14;16) (4,5) and del17p + gain1q (9,5). Clinical characteristics data at diagnosis according to HRC are shown in Table 1. Pts receiving 1st line were 100% (61), 90,2% of the pts received bortezomib (V) - based induction, of them 29% (n=16) were treated with alkylating agents, 49,1% (n=27) received IMIDs and 18,2% (n=10) V with dexamethasone (d), plus two of these pts received regimens composed of 3xVCd + 3xVPd and the other dara-VRd. 25 pts (40,98%) were transplant eligible (TPH). 2nd line, 32 pts (52,5%), (n=3) VTD-PACE, (n=6) daratumumab (n=1 alone, 3 R, 1 V, 1 K), (n=1) Kdexa, (n=1) Pocydex and (n=9) V plus 3 IMIDs, 2 alkylating, 2 P or 2 alone and (n=12) IMIDs and alkylatings in combination. 5 pts (8,2) were TPH (1 alogenic). 3rd line, 16 pts (26,2), just 3 pts were TPH. 4th line, 7 pts (11,4), 1 pts were TPH. 5th line, 4 pts (6,5). 6th line, 2pts (3,3). In the last lines, the use of triplets with pomalidomide, karfilzomib or intensive chemotherapy prevail. After a median follow-up of 3 y (IR 1,6-6,2) from diagnosis, pts had relapsed at least one time (60,6%) and more than 3 times (11,5%), and 25 had died (40,9%), 16 of them due to infections (14 bacteremia, 2 COVID), 5 cardiorespiratory arrest and 3 due to progression. (Image 1) represents PFS y OS for only 5 CA, as data were no representative in other CA. Correlation between ISS and ISS-R data were only able to execute in HRC gain1q, due to lack of sample in other CA. We found a P coefficient of 0.568399 or 56.83% (p- <0.00578, CI 95%). Summary/Conclusion: Our case series continues with a longer survival curve compared to those commented in other studies. As cytogenetic abnormalities (t(4;14), t(14;16), t(14;20) and gain1q), similar % of representation are described as Kumar. Nat Rev Clin Oncol. 2018, except for del(17p), 23% vs 10%. From the second line, the probability of receiving a new line, the duration of tto and the interval without tto decreased with each line of tto. As treatment lines progress, therapeutic combinations are more heterogeneous and less concordant. A further longer follow-up and higher HRC NDMM pts's recruitment will be necessary to clarify the response to tto regimens based on individual cytogenetic groups.