Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS

CORRESPONDENCE OPEN Da a umumab, ca filzomib, and dexame hasone in elapsed o e ac o y myeloma: final analysis o PLEIADES and EQUULEUS © The Au ho (s) 2023 Blood Cance Jou nal (2023) 13:33 ; h ps://doi.o g/ 10.1038/s41408-023-00805-x INTRODUCTION Da a umumab is app o ed in many coun ies as mono he apy and in combina ion egimens o elapsed/ e ac o y mul iple mye- loma (RRMM) and newly diagnosed mul iple myeloma [1–3]. Da a umumab-based combina ions ha e also demons a ed encou aging e ficacy in lenalidomide- e ac o y RRMM [4,5]. Ca filzomib is app o ed as mono he apy and in combina ion egimens, including da a umumab and dexame hasone (D-Kd), o RRMM [6]. In he phase 3 CANDOR s udy, D-Kd (in a enous [IV] da a umumab; ca filzomib 56 mg/m 2 wice weekly) imp o ed p og ession- ee su i al (PFS) e sus Kd in he o e all popula ion and lenalidomide- e ac o y pa ien s [7,8]. In he phase 3 A.R.R.O.W. s udy, once-weekly ca filzomib (70 mg/m 2 ) signifi- can ly p olonged PFS e sus wice-weekly ca filzomib (27 mg/m 2 ), p o iding a sa e and mo e con enien Kd dosing egimen [9]. P elimina y esul s om he phase 2 PLEIADES s udy (median ollow-up, 9.2 mon hs) and he phase 1b EQUULEUS s udy (median ollow-up, 16.6 mon hs) showed ha combining sub- cu aneous da a umumab (DARA SC) and da a umumab IV, espec i ely, wi h Kd (ca filzomib 70 mg/m 2 weekly) was well ole a ed and induced deep esponses in RRMM pa ien s [10,11]. We epo final da a om PLEIADES and EQUULEUS, wi h a median ollow-up o 12.4 and 23.7 mon hs, espec i ely. METHODS PLEIADES (ClinicalT ials.go Iden ifie : NCT03412565) e alua ed DARA SC (da a umumab 1800 mg co- o mula ed wi h ecombinan human hyalu onidase PH20 [ HuPH20; 2000 U/mL; ENHANZE ® d ug deli e y echnology, Halozyme, Inc., San Diego, CA, USA]) plus weekly Kd (ca filzomib 70 mg/m 2 ; dexame hasone 40 mg) in RRMM pa ien s wi h 1 p io line o lenalidomide-based he apy. EQUULEUS (NCT01998971) e alua ed da a umumab IV plus weekly Kd (ca filzomib 70 mg/m 2 ; dexame hasone 40 mg) in RRMM pa ien s a e 1 o 3 p io lines o he apy (including bo ezomib and an immunomodula o y d ug). Pa ien s in bo h s udies ecei ed 28-day cycles o D-Kd un il disease p og ession. P ima y endpoin s we e he o e all esponse a e (ORR) in PLEIADES and sa e y and ole abili y in EQUULEUS. Supplemen a y In o ma ion includes addi ional me hodology. RESULTS A o al o 66 and 85 pa ien s ecei ed D-Kd in PLEIADES and EQUULEUS, espec i ely. Pa ien demog aphic and baseline cha - ac e is ics a e summa ized in Table S1. In PLEIADES and EQUULEUS, he median ( ange) age was 61 (42–84) and 66 (38–85) yea s, espec i ely, 16/44 (36.4%) and 13/67 (19.4%) pa ien s had high- isk cy ogene ics, and 41 (62.1%) and 51 (60.0%) we e lenalidomide- e ac o y. Pa ien s in PLEIADES and EQUULEUS had ecei ed a median ( ange) o 1 (1–1) and 2 (1–4) p io lines o he apy, espec i ely, and 60 (90.9%) and 85 (100%) pa ien s had ecei ed p io p o easome inhibi o he apy. In PLEIADES and EQUULEUS, 31 (47.0%) and 50 (58.8%) pa ien s, espec i ely, discon inued ea men , p ima ily due o p og essi e disease. Median ( ange) ea men du a ion was 12.0 (0–21) mon hs in PLEIADES and 19.8 (0.3–34.5) mon hs in EQUULEUS. Pa ien disposi ion and d ug exposu e a e u he desc ibed in Supplemen a y In o ma ion. Pha macokine ic da a a e p o ided o pha macokine ic- e aluable popula ions (PLEIADES, n=65; EQUULEUS, n=85 [single fi s dose, n=10; spli fi s dose, n=75]). The maximum concen a ion o DARA SC was obse ed on Cycle 1, Day 4 a e he fi s dose o Cycle 3, Day 4 a e he nin h dose. Fo da a umumab IV, he maximum concen a ion was obse ed on Cycle 1, Day 1 (end o in usion) a e he fi s dose o Cycle 3, Day 1 (end o in usion) a e he nin h dose. In bo h s udies, se um ough concen a ion (C ough ) inc eased o maximum C ough on Cycle 3, Day 1 p e-dose, hen dec eased wi h less equen dosing. DARA SC p o ided nume ically highe C ough (wi hin a simila ange) e sus da a umumab IV. Subg oup analysis o se um da a umumab concen a ion based on body weigh in PLEIADES is p esen ed in Table S2. In EQUULEUS, pha macokine ic p ofiles o single and spli fi s da a umumab doses we e simila om Cycle 2, Day 1 p e- in usion onwa d (Table S3). No pa ien in he immunogenici y- e aluable popula ion o ei he s udy es ed posi i e o an i- da a umumab an ibodies. In PLEIADES, 3/64 (4.7%) pa ien s in he HuPH20 immunogenici y-e aluable popula ion had ea men - eme gen an i- HuPH20 an ibodies a e DARA SC adminis a ion; none we e neu alizing. The mos common any-g ade and g ade 3/4 ea men - eme gen ad e se e en s (TEAEs) in PLEIADES a e summa ized in Table 1. G ade 3/4 in ec ions occu ed in 9 (13.6%) pa ien s, mos commonly pneumonia (4.5%). Se ious TEAEs we e epo ed in 22 (33.3%) pa ien s, mos commonly pneumonia (4.5%). One (1.5%) pa ien discon inued ea men due o a TEAE. Th ee pa ien s had g ade 5 TEAEs: 1 each wi h COVID-19 pneumonia, sepsis, and espi a o y ailu e. The mos common any-g ade and g ade 3/4 TEAEs in EQUULEUS a e summa ized in Table 1. G ade 3/4 in ec ions we e epo ed in 18 (21.2%) pa ien s, mos commonly pneumonia (4.7%). Se ious TEAEs occu ed in 41 (48.2%) pa ien s, mos commonly basal cell ca cinoma, pneumonia, and uppe espi a- o y ac in ec ion (4.7% each). Fi e (5.9%) pa ien s discon inued ea men due o TEAEs. Th ee pa ien s had g ade 5 TEAEs: wo wi h gene al physical heal h de e io a ion and one wi h mul iple o gan dys unc ion synd ome. Two (3.0%) pa ien s in PLEIADES had g ade 3/4 ca diac TEAEs: one each wi h g ade 3 ca diac ailu e and g ade 4 le en icula Recei ed: 3 Oc obe 2022 Re ised: 24 Feb ua y 2023 Accep ed: 27 Feb ua y 2023 www.na u e.com/bcj Blood Cance Jou nal 1234567890();,: dys unc ion. In EQUULEUS, 9 (10.6%) pa ien s had g ade 3/4 ca diac TEAEs, including sinus achyca dia, ca diac ailu e, sys olic dys unc- ion (n=2 each) and a ial fib illa ion, conges i e ca diomyopa hy, le en icula ailu e, myoca dial ischemia, and myoca di is (n=1 each). In bo h s udies, he median le en icula ejec ion ac ion did no no ably change o e ime om baseline. Addi ional de ails a e included in Supplemen a y In o ma ion. Th ee (4.5%) pa ien s had in usion- ela ed eac ions (IRRs) wi h DARA SC in PLEIADES; wo had g ade 3 IRRs. All pa ien s wi h IRRs expe ienced hem on he fi s adminis a ion; he median ( ange) ime o IRR onse was 65 (4–75) min. Local injec ion-si e eac ions occu ed in 7 (10.6%) pa ien s; all we e g ade 1/2. In EQUULEUS, 6 (60.0%) pa ien s who ecei ed a single fi s dose and 31 (41.3%) who ecei ed a spli fi s dose had IRRs wi h da a umumab IV. Mos IRRs we e mild (2 pa ien s had g ade 3/4 IRRs) and occu ed du ing he fi s in usion. Fi e (50.0%) pa ien s expe ienced IRRs du ing Cycle 1, Day 1 wi h a single fi s da a umumab dose; 27 (36.0%) expe ienced IRRs du ing Cycle 1, Day 1 wi h a spli fi s da a umumab dose. In PLEIADES (median [ ange] ollow-up, 12.4 [0.2–20.6] mon hs), ORR was 84.8% in he all- ea ed popula ion and 84.1% in lenalidomide- e ac o y pa ien s (Fig. 1). ORR was 75.0% (12/16) and 82.1% (23/28) in pa ien s wi h high and s anda d cy ogene ic isk, espec i ely. The median du a ion o esponse was no Table 1. Mos common any-g ade (≥25%) and g ade 3/4 (≥5%) TEAEs wi h D-Kd in he PLEIADES and EQUULEUS s udies. PLEIADES D-Kd (n=66) EQUULEUS D-Kd (n=85) Any-g ade G ade 3/4 Any g ade G ade 3/4 TEAEs, n(%) 66 (100) 49 (74.2) 85 (100) 67 (78.8) Hema ologic Th ombocy openia 34 (51.5) 13 (19.7) 58 (68.2) 27 (31.8) Anemia 25 (37.9) 8 (12.1) 44 (51.8) 18 (21.2) Neu openia 15 (22.7) 7 (10.6) 26 (30.6) 18 (21.2) Lymphopenia 12 (18.2) 8 (12.1) 25 (29.4) 21 (24.7) Nonhema ologic Hype ension 23 (34.8) 14 (21.2) 28 (32.9) 17 (20.0) Insomnia 23 (34.8) 4 (6.1) 28 (32.9) 4 (4.7) Dia hea 20 (30.3) 0 32 (37.6) 2 (2.4) Nausea 17 (25.8) 0 36 (42.4) 1 (1.2) Nasopha yngi is 17 (25.8) 0 15 (17.6) 0 Headache 15 (22.7) 0 23 (27.1) 1 (1.2) Py exia 14 (21.2) 1 (1.5) 31 (36.5) 1 (1.2) As henia 14 (21.2) 0 36 (42.4) 13 (15.3) Cough 13 (19.7) 0 24 (28.2) 0 Dyspnea 12 (18.2) 1 (1.5) 30 (35.3) 3 (3.5) Uppe espi a o y ac in ec ion 12 (18.2) 0 38 (44.7) 3 (3.5) Vomi ing 11 (16.7) 0 34 (40.0) 1 (1.2) D-Kd da a umumab/ca filzomib/dexame hasone, TEAE ea men -eme gen ad e se e en . PRVGPRCRsCR PLEIADES D-Kd (n = 66) PLEIADES D-Kd lenalidomide- e ac o y (n = 44) EQUULEUS D-Kd (n = 85) EQUULEUS D-Kd lenalidomide- e ac o y (n = 51) 0 20 40 60 80 100 ORR, % 19.7 22.7 34.8 7.6 18.2 18.2 36.4 11.4 21.2 14.1 32.9 12.9 17.6 13.7 33.3 9.8 84.8% 84.1% 81.2% 74.5% ≥CR: 42.4% ≥VGPR: 77.3% ≥CR: 36.4% ≥VGPR: 72.7% ≥CR: 35.3% ≥VGPR: 68.2% ≥CR: 31.4% ≥VGPR: 64.7% Fig. 1 Response a es in all pa ien s and lenalidomide- e ac o y pa ien s ea ed wi h D-Kd in PLEIADES o EQUULEUS. Da a we e shown o he all- ea ed popula ion. No e: Due o ounding, pe cen ages may no add up o he o al pe cen age o each ca ego y. CR comple e esponse, D-Kd da a umumab/ca filzomib/dexame hasone, ORR o e all esponse a e, PR pa ial esponse, sCR s ingen comple e esponse, VGPR e y good pa ial esponse. Co espondence 2 Blood Cance Jou nal (2023) 13:33 eached; he 9-mon h du a ion o esponse a e was 85.4%. PFS and o e all su i al (OS) we e no analyzed. In EQUULEUS (median [ ange] ollow-up, 23.7 [0.5–34.7] mon hs), ORR was 81.2% in he all- ea ed popula ion and 74.5% in lenalidomide- e ac o y pa ien s (Fig. 1). The median du a ion o esponse was 27.5 mon hs; he 9-mon h du a ion o esponse a e was 88.3%. Median PFS was 25.7 mon hs in he all- ea ed popula ion (Fig. S1A) and 22.3 mon hs in lenalidomide- e ac o y pa ien s; es ima ed 24-mon h PFS a es we e 52.7% and 46.9%, espec i ely. The median ime o subsequen an i-cance he apy was 29.2 mon hs. Median OS was no eached; he es ima ed 24- mon h OS a e was 71.2% (Fig. S1B). DISCUSSION Wi h addi ional ollow-up in PLEIADES and EQUULEUS, no new sa e y conce ns we e iden ified, and he o e all sa e y p ofile o D-Kd was consis en be ween s udies. As p e iously demons a ed, lowe IRR a es and sho e adminis a ion imes we e obse ed wi h he DARA SC–based e sus da a umumab IV–based egimen. In EQUULEUS, spli fi s da a umumab dosing p oduced simila sa e y and pha macokine ic p ofiles as a single fi s dose om Cycle 2, Day 1 p e-in usion onwa d and dec eased median in usion du a ion on Cycle 1, Day 1, which may imp o e pa ien con enience. Following weekly dosing, C ough o da a umumab a Cycle 3, Day 1 p e-dose was nume ically highe (wi hin a simila ange) wi h DARA SC e sus da a umumab IV. DARA SC adminis a ion achie ed adequa e and consis en exposu e o all body weigh subg oups. The incidence o ea men -eme gen an i-da a umumab an ibodies was 0% in bo h s udies, indica ing a low isk o immunogenici y o D-Kd. The incidence o ea men -eme gen HuPH20 an ibodies was consis- en wi h o he DARA SC s udies [12,13]. Final analysis esul s om bo h s udies showed D-Kd consis- en ly induced deep esponses ega dless o lenalidomide e ac o iness. ORRs in PLEIADES and EQUULEUS we e compa - able (84.8% and 81.2%, espec i ely). Encou aging 24-mon h PFS and OS a es o 52.7 and 71.2%, espec i ely, we e demons a ed in EQUULEUS. C oss- ial compa isons should be in e p e ed cau iously due o s udy di e ences. The phase 3 CANDOR s udy [8] compa ed da a umumab IV plus Kd e sus Kd in RRMM pa ien s wi h 1 o 3 p io lines o he apy. Pa ien s in CANDOR ecei ed ca filzomib 56 mg/m 2 wice weekly (mon hly cumula i e dose, 336 mg/m 2 [Cycle 1, 264 mg/m 2 ]), while pa ien s in PLEIADES and EQUULEUS ecei ed ca filzomib 70 mg/m 2 weekly (mon hly cumula i e dose, 210 mg/m 2 [Cycle 1, 160 mg/m 2 ]; ie, 62.5% o CANDOR mon hly dose). A highe p opo ion o pa ien s in PLEIADES and EQUULEUS had p io lenalidomide exposu e (100% and 95%, espec i ely) o we e e ac o y o lenalidomide (62% and 60%) e sus he CANDOR D-Kd a m (39% and 32%, espec i ely). ORRs in PLEIADES (84.8%) and EQUULEUS (81.2%) we e compa able o ha epo ed a a median ollow-up o 27.8 mon hs in he CANDOR D-Kd a m (84%), wi h highe comple e esponse o be e a es (42.4% and 35.3% s 33%, espec i ely). Median PFS was simila be ween he D-Kd a ms o EQUULEUS and CANDOR (25.7 and 28.6 mon hs, espec i ely) [8]. O e all, D-Kd demons a ed e ficacy in PLEIADES, EQUULEUS, and CANDOR, suppo ing i s use o RRMM, including lenalidomide- e ac o y mul iple myeloma. Sa e y p ofiles we e gene ally simila wi h D-Kd u ilizing weekly ca filzomib dosing in PLEIADES and EQUULEUS and wice-weekly ca filzomib dosing in CANDOR; howe e , he incidence o a al TEAEs was lowe in PLEIADES (3/66 [4.5%]) and EQUULEUS (3/85 [3.5%]) compa ed o he CANDOR D-Kd a m (27/308 [8.8%]) [8]. Resul s om he phase 3 A.R.R.O.W. s udy also ein o ce he a o able benefi - isk p ofile o once-weekly ca filzomib dosing compa ed wi h a wice-weekly ea men schedule [9]. Once-weekly ca filzomib dosing may imp o e cos -e ec i eness and con enience o pa ien s and heal hca e p o ide s [14]. Limi a ions o PLEIADES and EQUULEUS include small sample sizes and lack o compa a o a ms. Also, pa ien s in PLEIADES we e only ollowed o up o 8 weeks a e he las s udy ea men ; he e o e, PFS and OS we e no e alua ed. In conclusion, D-Kd con inues o be well ole a ed and e ec i e in RRMM pa ien s, including lenalidomide- e ac o y pa ien s. Final analysis esul s om PLEIADES and EQUULEUS u he suppo D-Kd as a s anda d ea men egimen o RRMM. Philippe Mo eau 1 ✉, Ajai Cha i 2 , Albe O iol 3 , Joaquin Ma inez-Lopez 4 , Ma hias Haenel 5 , Cy ille Touzeau 1 , Sikande Ailawadhi 6 , B i a Beseme 7 , Ja ie de la Rubia Comos 8,9 , C is ina Encinas 10 , Ma ia-Vic o ia Ma eos 11 , Hans Salwende 12 , Paula Rod iguez-O e o 13 , Cy ille Hulin 14 , Lionel Ka lin 15 , Anna Su eda Bala i 16 , Joan Ba gay 17 , Lo fiBenboubke 18 , Lau a Rosiñol 19 , S e ano Ta an olo 20 , Howa d Te ebelo 21 , Shiyi Yang 22 , Jianping Wang 22 , I o Nnane 22 , Ming Qi 22 , Michele Kosh 22 , Ma ia Delioukina 22 and Ha mu Goldschmid 23 1 Hema ology, Uni e si y Hospi al Hô el-Dieu, Nan es, F ance. 2 Icahn School o Medicine a Moun Sinai, New Yo k, NY, USA. 3 Ins i u Ca alà d’Oncologia and Ins i u Josep Ca e as, Hospi al Ge mans T ias i Pujol, Ba celona, Spain. 4 Hospi al 12 de Oc ub e, H12O-CNIO, Haema ological Malignancies Clinical Resea ch Uni , Uni e sidad Complu ense, CIBERONC, Mad id, Spain. 5 Klinikum Chemni z, Chemni z, Ge many. 6 Mayo Clinic Flo ida, Jackson ille, FL, USA. 7 Uni e si ae sklinikum Tuebingen de Ebe ha d-Ka ls-Uni e si ae , Ab eilung ue Inne e Medizin II, Tübingen, Ge many. 8 Hospi al La Fe, School o Medicine and Den is y, Ca holic Uni e si y o Valencia, Valencia, Spain. 9 CIBERONC, Ins i u o Ca los III, Mad id, Spain. 10 Hospi al Gene al Uni e si a io G ego io Ma añón (HGUGM), IiSGM, Mad id, Spain. 11 Uni e si y Hospi al o Salamanca/IBSAL/Cance Resea ch Cen e -IBMCC (USAL-CSIC), Salamanca, Spain. 12 Asklepios Tumo zen um Hambu g, AK Al ona and AK S . Geo g, Hambu g, Ge many. 13 Clínica Uni e sidad de Na a a, Pamplona, Spain. 14 Depa men o Hema ology, Hôpi al Hau Lé êque, Uni e si y Hospi al, Pessac, F ance. 15 Depa men o Hema ology, Cen e Hospi alie Lyon Sud, Hospices Ci ils de Lyon, Pie e-Béni e, F ance. 16 Hema ology Depa men , Ins i u Ca alà d’Oncologia - Hospi ale , IDIBELL, Uni e si y o Ba celona, Ba celona, Spain. 17 Hospi al Uni e si a i Son Llà ze , IdISBa, Palma de Mallo ca, Illes Balea s, Spain. 18 Se ice d’Héma ologie e Thé apie Cellulai e, Hôpi al B e onneau, Cen e Hospi alie Régional Uni e si ai e (CHRU), Tou s, F ance. 19 Hospi al Clínic de Ba celona, IDIBAPS, Ba celona, Spain. 20 Neb aska Cance Specialis s, Omaha, NE, USA. 21 P o idence Cance Cen e , Sou hfield, MI, USA. 22 Janssen Resea ch & De elopmen , LLC, Sp ing House, PA, USA. 23 GMMG-S udy G oup a Uni e si y Hospi al Heidelbe g, In e nal Medicine V, Heidelbe g, Ge many. ✉email: philippe.mo eau@chu-nan es. 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Subcu aneous e sus in a enous da a umumab in pa ien s wi h elapsed o e ac o y mul iple myeloma (COLUMBA): a mul icen e, open-label, non-in e io i y, andomised, phase 3 ial. Lance Haema ol. 2020;7:e370–80. 14. Kuma SK, Maje I, Panjabi S, Medheka R, Campioni M, Dimopoulos MA. Cos - e ec i eness o once weekly ca filzomib 70 mg/m 2 plus dexame hasone in pa ien s wi h elapsed and e ac o y mul iple myeloma in he Uni ed S a es. Expe Re Hema ol. 2020;13:687–96. ACKNOWLEDGEMENTS These s udies (ClinicalT ials.go Iden ifie s: NCT03412565 and NCT01998971) we e sponso ed by Janssen Resea ch & De elopmen , LLC. We hank he pa ien s pa icipa ing in he PLEIADES and EQUULEUS s udies and hei amilies, he s a membe s a he s udy si es, he da a and sa e y moni o ing commi ees, and he s a membe s who we e in ol ed in he da a collec ion and analyses. We also hank Amgen o supplying he ca filzomib used in hese s udies. Medical w i ing and edi o ial suppo we e p o ided by Lisa Shannon, Pha mD, o Lumani y Commu- nica ions Inc., and we e unded by Janssen Global Se ices, LLC. AUTHOR CONTRIBUTIONS All au ho s in e p e ed he da a, e iewed he manusc ip , app o ed he final e sion, decided o publish his epo , and ouch o he da a accu acy and comple eness. COMPETING INTERESTS PM ecei ed hono a ia om B is ol Mye s Squibb/Celgene, Janssen-Cilag, AbbVie, Amgen, Takeda, Oncopep ides, Sanofi, and GlaxoSmi hKline. AC se ed as a consul an o in an ad iso y ole o Amgen, Janssen Oncology, Sea le Gene ics, Ka yopha m The apeu ics, Genzyme, Oncopep ides, Takeda, An engene, GlaxoS- mi hKline, Secu a Bio, Sha uck Labs, Genen ech, AbbVie, and B is ol Mye s Squibb/ Celgene; and ecei ed esea ch unding om Celgene, Janssen, Amgen, Sea le Gene ics, Takeda, and Pha macyclics. AO se ed on ad iso y boa ds o Sanofi, GlaxoSmi hKline, B is ol Mye s Squibb, Amgen, and Janssen. JM-L consul ed o , ecei ed hono a ia om, and se ed on a boa d o di ec o s o ad iso y commi ees o Janssen; consul ed o and ecei ed esea ch unding om B is ol Mye s Squibb and Incy e; and consul ed o No a is. MH ecei ed hono a ia om Amgen, No a is, Roche, Celgene, Takeda, and Baye . CT ecei ed hono a ia om and se ed in a consul ing o ad iso y ole o Janssen, Celgene, Takeda, Amgen, and AbbVie; and had a el, accommoda ions, o o he expenses paid o eimbu sed by Janssen, Takeda, Amgen, and AbbVie. SA se ed as a consul an o GlaxoSmi hKline, Sanofi, B is ol Mye s Squibb, Takeda, BeiGene, Pha macyclics, Amgen, and Janssen; and ecei ed esea ch unding om GlaxoSmi hKline, B is ol Mye s Squibb, Pha macyclics, Amgen, Janssen, Cellec a , Xenco , and AbbVie. BB ecei ed hono a ia om Janssen, Amgen, Takeda, and Sanofi. JdlRC ecei ed hono a ia om B is ol Mye s Squibb/ Celgene, Jansen-Cilag, Amgen, Takeda, Sanofi, and GlaxoSmi hKline; and ecei ed a el suppo om Janssen-Cilag. CE ecei ed hono a ia om B is ol Mye s Squibb/ Celgene, Janssen-Cilag, Amgen, Sanofi, and GlaxoSmi hKline. M-VM ecei ed hono a ia de i ed om lec u es and pa icipa ion in ad iso y boa ds om Janssen, Celgene, Takeda, Amgen, GlaxoSmi hKline, AbbVie, Pfize , Regene on, Adap i e Bio echnologies, Roche, and Sea le Genen ech. HS ecei ed hono a ia om B is ol Mye s Squibb/Celgene, Janssen-Cilag, AbbVie, Amgen, Takeda, Oncopep ides, Sanofi, and GlaxoSmi hKline; and ecei ed a el suppo om B is ol Mye s Squibb/Celgene, Janssen-Cilag, AbbVie, Amgen, Sanofi, and GlaxoSmi hKline. PR-O pa icipa ed in speake s bu eaus o and ecei ed hono a ia om B is ol Mye s Squibb/Celgene, Janssen, Amgen, GlaxoSmi hKline, Sanofi, Regene on, and Oncopep ides. CH ecei ed hono a ia om Janssen, B is ol Mye s Squibb, Amgen, Takeda, and AbbVie. LK se ed on ad iso y boa ds o and/o ecei ed hono a ia o a el suppo om Celgene/B is ol Mye s Squibb, Janssen, Takeda, Amgen, and GlaxoSmi hKline. ASB se ed as a consul an o , ecei ed hono a ia om, and pa icipa ed in speake s bu eaus o Takeda. LR ecei ed hono a ia om Janssen, Celgene, Amgen, Takeda, Sanofi, and GlaxoSmi hKline. HT se ed on an ad iso y boa d o B is ol Mye s Squibb; and pa icipa ed in speake s bu eaus o ADP. SY, JW, IN, MQ, and MK a e employees o Janssen Resea ch & De elopmen , LLC, and may hold equi y. MD was employed by Janssen Resea ch & De elopmen , LLC, a he ime o he s udy. HG ecei ed g an s and/o p o ision o In es iga ional Medicinal P oduc s om Amgen, B is ol Mye s Squibb, Celgene, Chugai, Die ma Hopp Founda ion, Janssen, Johns Hopkins Uni e si y, and Sanofi; ecei ed esea ch suppo om Amgen, B is ol Mye s Squibb, Celgene, Chugai, Janssen, Incy e, Molecula Pa ne s, Me ck Sha p & Dohme, Sanofi, Mundipha ma GmbH, Takeda, and No a is; se ed on ad iso y boa ds o Adap i e Bio echnologies, Amgen, B is ol Mye s Squibb, Celgene, Janssen, Sanofi, and Takeda; and ecei ed hono a ia om Amgen, B is ol Mye s Squibb, Celgene, Chugai, GlaxoSmi hKline, Janssen, No a is, and Sanofi. JB, LB, and ST ha e no hing o disclose. ADDITIONAL INFORMATION Supplemen a y in o ma ion The online e sion con ains supplemen a y ma e ial a ailable a h ps://doi.o g/10.1038/s41408-023-00805-x. Co espondence and eques s o ma e ials should be add essed o Philippe Mo eau. 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To iew a copy o his license, isi h p:// c ea i ecommons.o g/licenses/by/4.0/. © The Au ho (s) 2023 Co espondence 4 Blood Cance Jou nal (2023) 13:33