Furthermore data within the interference of anti\CD38 antibodies with blood compatibility testing suggest that daratumumab can persist in the individuals plasma for up to at least 6?weeks after the last infusion (Oostendorp em et?al /em , 2015; vehicle de Donk em et?al /em , 2016). daratumumab treatment may enable individuals to recover from previous lines of treatment and receive full dosing of subsequent therapies. In conclusion, a high proportion of RRMM individuals benefitted from retreatment with IMiDs and PIs after daratumumab treatment. These retreatment options should consequently become explored in RRMM individuals progressing on daratumumab monotherapy. retinoic acid; IMiD, immunomodulatory drug; PI, proteasome inhibitor; RRMM, relapsed/refractory multiple myeloma. Reactions to IMiD retreatment in IMiD\refractory individuals after daratumumab In the 29 IMiD\refractory individuals retreated with an IMiD\centered routine after daratumumab the ORR was 52% (15/29 individuals: 13 PR and 2 very good partial response [VGPR]). Nine individuals (31%) showed no response and therapy was halted after a maximum of 3 cycles because of PD, furthermore 1 individual showed stable disease (SD) and 4 individuals experienced a MR. In total 20/29 individuals (69%) therefore experienced an improvement in comparison to the PD upon their earlier IMiD treatment. In several instances however a different IMiD, and in many cases a different routine and/or a different dose was used in the post\daratumumab treatment. Table?1 and Fig?2 provide detailed info on IMiD retreatment in the IMiD\refractory daratumumab\treated individuals. The median time interval between the last IMiD prior to daratumumab and daratumumab imitation was 3?months, with a maximum of 23?weeks. The median time interval between daratumumab cessation and subsequent IMiD treatment was 1?month, in three individuals this time interval was longer than 1?yhearing. Some individuals Atractyloside Dipotassium Salt were given additional therapies between the IMiD and daratumumab treatments. Table 1 Characteristics of IMiD treatment before and after daratumumab treatment in IMiD refractory individuals thead valign=”top” th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Patient /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ IMiD\refractory /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Last IMiD before dara /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Interval IMiD\dara (weeks) Atractyloside Dipotassium Salt /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Response to dara /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ First IMiD after Atractyloside Dipotassium Salt dara /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Interval dara\IMiD (weeks) /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Response to IMiD after dara /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ PFS for IMiD after dara (weeks, reason RIEG for discontinuation) /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Improved response to IMiD post\dara /th /thead 1lenalena (MPR\R maintenance, 10?mg)10PDlena (len\dex, 25?mg)1MR2 (progression)yes2lenalena (RAD, 25?mg)3SDlena (REP, 25?mg)1MR16+ (ongoing)yes (same dose)3lena, thallena (REP)1SDthal (TAD\bor, 100?mg)1MR2 (progression)yes4lena, thal, pomapoma (pom\dex)23PRpoma (pom\carf\dex, dose unfamiliar)4MR3 (progression)yes5lenalena (len\dex)1PDlena (KRd)1PD0 (progression)no6lenalena (len\dex)1PDlena (REP)1PD0 (progression)no7lenalena (len\dex)2PDlena (VRD)1PD0 (progression)no8lenalena (REP)1PRpoma (pom\dex)1PD0 (progression)no9lenalena (REP)3SDpoma (pom\dex)1PD0 (progression)no10lenalena (RAD)27PDthal (VTD)2PD0 (progression)no11lenalena (benda\len\dex)2PDthal (VTD)1PD0 (progression)no12lena, thallena (REP)2SDlena (len\dex)1PD0 (progression)no13thallena (REP)1CRlena (len\dex)1PD0 (progression)no14lenalena (REP, 10?mg)16PDpoma (pom\dex, 4?mg)1PR7 (progression)yes15lenalena (VRD, 10?mg)1SDlena (len\dex, 25?mg)19PR37 (progression)yes16lena (len\dex, 25?mg)thal (VTD)5PRlena (REP, 10?mg)1PR1 (death due to illness)yes17lenalena (len\dex, 15?mg)4PDlena (REP, 15?mg)1PR7 (death due to illness)yes18lenalena (len\dex, 10?mg)6PRlena (REP, 10?mg)27PR5 (progression)yes19lenalena (VRD)2PRpoma (pom\dex, 4?mg)13PR4 (progression)yes20lenalena (REP)2PRpoma (pom\dex, 4?mg)1PR10 (progression)yes21lenalena (REP)3PRpoma (pom\dex, 4?mg)2PR5 (progression)yes22lena, pomapoma (pom\dex)n.a.PDlena (RAD, dose unknown)1PR8 (progression)yes23lena, pomapoma (pom\dex)1PDthal (VTD, 100?mg)1PR5 (progression)yes24lena, thallena (MPR, 15?mg)3VGPRlena (len\dex, 15?mg)1PR9 (progression)yes (same dose)25lena (mono, 10?mg), thalthal (thal\dex, dose unknown)5SDlena (len\dex, 25?mg)1PR14 (progression)yes26lena, thallena (len\dex, 25?mg)17PDlena (REP, 25?mg)1PR3 (death due to illness)yes27lenalena (REP, 25?mg)1PDlena (len\dex, 25?mg)1SD3 (progression)yes (same dose)28lenalena (VRED, 10?mg)2CRlena (VRD, 25?mg)1VGPR4 (progression)yes29lena, thallena (REP, 15?mg)10SDlena (len\dex, 25?mg)1VGPR12 (progression)yes Open in a separate windows benda, bendamustine; CR, total remission; dara, daratumumab; dex, dexamethasone; IMiD, immunomodulatory drug; KRd, carfilzomib, lenalidomide, dexamethasone; lena, lenalidomidemono, monotherapy; MPR(\R), melphalan, prednisone, lenalidomide (+rituximab); MR, minimal response; PD, progressive disease; PFS, progression free survival; poma, pomalidomide; PR, partial response; RAD, lenalidomide, adriamycin, dexamethasone; REP, lenalidomide, cyclophosphamide, prednisone; SD, stable disease; TAD, thalidomide, adriamycin, dexamethasone; thal, thalidomide; VGPR, very good partial response; VRD, bortezomib, lenalidomide, dexamethasone; VRED, bortezomib, lenalidomide, cyclophosphamide, dexamethasone; VTD, bortezomib, thalidomide, dexamethasone. Open in a separate window Number 2 Effectiveness of IMiD treatment after daratumumab in IMiD\refractory individuals. (A) 29 IMiD\refractory individuals were retreated with an IMiD\centered regimen, leading to an ORR of 52% (PR or better, 15/29 individuals). (B) Distribution of reactions in the IMiD\refractory individuals. (C) Distribution of variable and similar treatment mixtures and doses in the twenty individuals achieving SD or better upon IMiD retreatment.IMiD, immunomodulatory drug; MR, minimal response; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response. [Colour figure can be viewed at http://wileyonlinelibrary.com] Four.