key words: bortezomib, multiple myeloma, retrospective analysis, treatment outcomes, subcutaneous, intravenous

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1 reserch report Effect of Route of Bortezomib Administrtion on Tretment Outcomes in Previously Untreted Ptients with Multiple Myelom: A Retrospective Anlysis from US Community Oncology Prctices Robert M Rifkin, MD, FACP; 1 Esprit M, MPH; 2,3 Robyn Hrrell, MS; 1 Lin Asmr, PhD; 1 Ynyn Zhu, PhD, MPH; 2 Liviu Niculescu, MD; 2 Vijyveer Bonthplly, PhD 2 ffilitions: 1 McKesson Specilty Helth The US Oncology Network, The Woodlnds, TX 2 Millennium Phrmceuticls, Inc., wholly owned subsidiry of Tked Phrmceuticl Compny Limited, Cmbridge, MA 3 Institute for Clinicl Reserch nd Helth Policy Studies, Tufts Medicl Center, Boston, MA ddress correspondence to: Robert M Rifkin, MD, FACP McKesson Specilty Helth The US Oncology Network The Woodlnds, TX Phone: Fx: Emil: Robert.Rifkin@USONCOLOGY.COM bstrct: A phse 3 study (MMY-3021) in relpsed/refrctory multiple myelom (MM) demonstrted non-inferior efficcy nd n improved systemic sfety profile with subcutneous (SC) versus intrvenous (IV) bortezomib. The present retrospective observtionl study used popultion-level dt from the iknowmed electronic helth records dtbse within McKesson Specilty Helth The US Oncology Network to evlute the impct of bortezomib dministrtion route on tretment outcomes in ptients with previously untreted MM. Bseline chrcteristics were similr between ptients who received solely IV or SC bortezomib (436 nd 379 ptients, respectively), except in rte of generl comorbidities. A shorter medin durtion of tretment (116 vs 142 dys; P = 0.019), trend for more dose reductions t 16 weeks (13% vs 11%; P = 0.27), nd shorter medin time to dose reduction (49 vs 56 dys; P = 0.30) were observed with IV versus SC dministrtion. Similr 2-yer survivl rtes were observed (78% vs 79%). Overll, our findings suggest similr tretment outcomes nd the potentil for improved tolerbility with SC versus IV bortezomib s initil therpy in the clinicl setting. key words: bortezomib, multiple myelom, retrospective nlysis, tretment outcomes, subcutneous, intrvenous cittion: Journl of Clinicl Pthwys. 2016;2(2): Received Februry 16, 2016; Accepted Februry 23, Bortezomib is the first-in-clss protesome inhibitor pproved for the tretment of multiple myelom (MM) in the United Sttes nd Europen Union. 1,2 The phse 3, interntionl MMY-3021 study in relpsed/refrctory MM demonstrted non-inferior efficcy between subcutneous (SC) nd intrvenous (IV) bortezomib on the mesures of response rte fter 4 cycles, time to progression, progression-free survivl (PFS), nd overll survivl (OS). An improved systemic sfety profile with SC bortezomib ws demonstrted, with disclosures: Robert Rifkin is member of dvisory committees for Celgene Corportion, Millennium Phrmceuticls, Inc., Cmbridge, MA, USA, wholly owned subsidiry of Tked Phrmceuticl Compny Limited, nd Onyx Phrmceuticls, subsidiry of Amgen. Esprit M is former employee of nd hs stock or ownership interest in Millennium Phrmceuticls, Inc., Cmbridge, MA, USA, wholly owned subsidiry of Tked Phrmceuticl Compny Limited. Robyn Hrrell is n employee of nd hs stock or ownership interest in McKesson Specilty Helth. Lin Asmr is n employee of McKesson Specilty Helth. Ynyn Zhu is n employee of Millennium Phrmceuticls, Inc., Cmbridge, MA, USA, wholly owned subsidiry of Tked Phrmceuticl Compny Limited. Liviu Niculescu is n employee of Millennium Phrmceuticls, Inc., Cmbridge, MA, USA, wholly owned subsidiry of Tked Phrmceuticl Compny Limited nd hs stock or ownership interest in Millennium Phrmceuticls, Inc., Cmbridge, MA, USA, wholly owned subsidiry of Tked Phrmceuticl Compny Limited, nd Pfizer. Vijyveer Bonthplly is n employee of nd hs stock or ownership interest in Millennium Phrmceuticls, Inc., Cmbridge, MA, USA, wholly owned subsidiry of Tked Phrmceuticl Compny Limited. cknowledgements: The uthors would like to cknowledge the writing support of Steve Hill nd Ctherine Crookes of FireKite, n Ashfield Compny, prt of UDG Helthcre PLC, in the development of this mnuscript, which ws funded by Millennium Phrmceuticls, Inc., nd Jnssen Globl Services, LCC, nd complied with Good Publiction Prctice Ethicl Guidelines (Bttisti WP, et l: Ann Intern Med 163:461-4, 2015). This nlysis ws funded by Millennium Phrmceuticls, Inc. Mrch 2016 Journl of Clinicl Pthwys 35

2 significntly lower rtes of peripherl neuropthy compred with IV dministrtion. 3,4 This resulted in the pprovl of SC injection s n dditionl route of bortezomib dministrtion in The improved systemic sfety profile of SC bortezomib demonstrted in the MMY-3021 study 4 ws further supported in recent review of clinicl dt on SC bortezomib by Petrucci et l. 5 Notbly, severl studies hve shown tht twice-weekly or weekly SC dministrtion of bortezomib is generlly well tolerted in newly dignosed s well s relpsed/refrctory MM ptients, 6-18 including elderly ptients who re typiclly more sensitive to the side effects of tretment. 10,13,19 SC bortezomib is lso preferred compred with IV dministrtion by mjority of ptients 20,21 nd is lso esier to dminister. 6,7,20,21 Severl individul studies hve lso generlly supported the ssocition of low rte of peripherl neuropthy with SC dministrtion. 6,8-12,14,18,22-24 The non-inferior efficcy nd better tolerbility with SC dministrtion of bortezomib, s reported to dte, hve the potentil to impct tretment outcomes in the clinicl setting. However, there is pucity of comprtive effectiveness dt on SC versus IV bortezomib s initil therpy in MM outside of the clinicl tril setting. Therefore, the min objective of this study ws to determine the impct of route of bortezomib dministrtion on tretment outcomes in previously untreted MM ptients in the community oncology setting. methods This ws non-interventionl, retrospective, observtionl cohort study using popultion-level dt from n electronic helth records (EHR) dtbse. Key inclusion criteri for the trget ptient popultion were: newly dignosed MM (ICD-9: ); ge 18 yers; no prior chemotherpy before initition of bortezomib-bsed tretment; initition of bortezomib-bsed tretment during the study identifiction period (Jnury 1, 2011 to November 30, 2012); nd 2 MM-relted visits. In order to reflect routine clinicl prctice in MM, the nlysis excluded ptients enrolled in rndomized clinicl trils nd those with other cncer dignoses. Ptients were originlly followed through My 31, 2013 to llow minimum 6-month observtionl window; however, some ptients were lost to follow-up prior to 6 months (rnge, months). The follow-up period ws updted through July 31, This study ws conducted in ccordnce with the principles of the Declrtion of Helsinki nd with pprovl of the centrl Institutionl Review Bord t the US Oncology Network (USON). Dt Source Dt were collected vi progrmmtic dt queries of the iknowmed (ikm) EHR dtbse within the McKesson Specilty Helth USON (MSH USON). ikm cptures dt on outptient medicl oncology cre for ptients treted cross 19 sttes in the United Sttes. Overll, the system cptures dt on pproximtely 10% of newly dignosed cncer ptients in the United Sttes. Dt collected from ikm EHR for this study included ptient demogrphics nd clinicl chrcteristics t bseline nd dt on bortezomib tretment exposure, including route(s) of dministrtion nd dose. Pyer sttus nd dt on clims for services provided within the MSH USON were obtined from US Oncology s finncil dt wrehouse. Dt Anlysis Anlyses were conducted on per-protocol bsis to evlute ny direct ssocition between the route of dministrtion nd tretment exposure/outcomes. The per-protocol popultion comprised those ptients who received bortezomib solely through IV or SC dministrtion, nd excluded ny ptients who switched route of dministrtion. An lgorithm ws employed to stndrdize dt on initil bortezomib doses per the bortezomib prescribing informtion: 2 first doses of 1.5 mg/m 2 were djusted to the 1.5 mg/m 2 dose level; doses of 1.3 mg/m 2 but < 1.5 mg/m 2 were djusted to the 1.3 mg/m 2 dose level; doses of 1.0 mg/m 2 but < 1.3 mg/m 2 were djusted to the 1.0 mg/m 2 dose level; nd doses of < 1.0 mg/m 2 were djusted to the 0.7 mg/m2 dose level. Among ptients with dose reductions, ptients subsequent doses with t lest 10% chnge from initil dose during tretment were djusted to the stndrdized dose rnge of 0.7 to 1.5 mg/m 2. Dose reductions nd time to dose reduction dt were cptured t three time points: 16 weeks, 24 weeks, nd 32 weeks. These time points were selected to correspond with bortezomib cycle length of 3 5 weeks nd with ptient follow-up visits, which typiclly occur monthly. Between-group comprisons were conducted using the chi-squre test for ctegoricl vribles nd using the Fisher exct test for sprse dt. For comprison of continuous vribles, t tests or nonprmetric Wilcoxon-Mnn-Whitney tests were used. Univrite nd multivrite Cox proportionl hzrds regression model of time to dose reduction ws used to identify sttisticlly significnt covrites (including route of dministrtion, ge, gender, body mss index, prctice region, pyer sttus, Interntionl Stging System stge, MM subtype, bseline score on the Krnofsky Performnce Sttus Scle, receipt of stem-cell trnsplnt, initil dose, bseline comorbidity, nd chemotherpy bckbone). Time to event dt, including time to dose reduction nd OS, were estimted in the overll popultion using the Kpln-Meier method. results A totl of 1058 ptients dignosed with MM who hd no previous chemotherpy nd who initited IV or SC bortezomib during the study identifiction period (Jnury 1, Journl of Clinicl Pthwys Mrch

3 MM ptients, N = 15,534 MM ptients included in nlysis, N = 13,612 Excluded, n = 1922 (12%): Ptients treted in RCT, n = 639 Ptients with other cncer, n = 1332 Excluded, hd not been treted with bortezomib, n = 7547 (55%) MM ptients treted with bortezomib in study period, N = 6065 (45%) Excluded, treted with bortezomib in lter line of therpy or line of therpy informtion missing, n = 4403 (73%) MM ptients treted with bortezomib in first-line setting in study period, N = 1662 (27%) Excluded, received chemotherpy prior to first-line bortezomib, n = 604 (36%) Previously untreted MM ptients inititing bortezomib in study period with no previous chemotherpy, N = 1058 (64%) Per-protocol popultion: received only IV or only SC bortezomib, N = 815 (77%) Switchers popultion, n = 243: Received IV then SC bortezomib, n = 216; 33 switched bck Received SC then IV bortezomib, n = 27; 12 switched bck Received IV bortezomib n = 436 Received SC bortezomib n = 379 Figure 1. Ptient Flow Digrm Forty-nine ptients overlpped between two exclusion criteri of enrollment in n RCT nd dignosis of other primry cncer. Abbrevitions: IV, intrvenous; MM, multiple myelom; RCT, rndomized controlled tril; SC, subcutneous. Mrch 2016 Journl of Clinicl Pthwys 37

4 to November 30, 2012) were included. Of these ptients, 243 switched route of bortezomib dministrtion during tretment (216 received IV then switched to SC; 27 received SC then switched to IV) nd were excluded. Of the 815 ptients who did not switch route of dministrtion, 436 (53%) received IV bortezomib nd 379 (47%) received SC bortezomib (Figure 1). At bseline, ptient demogrphics nd clinicl chrcteristics were brodly similr between the IV nd SC groups (Tble 1). However, the rte of generl comorbidities t bseline, which included weight loss, norexi, dehydrtion, dirrhe, dyspne, hypervolemi, mlise, nuse, pin, nd sepsis, ws significntly higher in the IV thn in the SC group (22% vs 15%; P = ). Similr proportions of ptients receiving IV bortezomib nd SC bortezomib underwent stem-cell trnsplnt t ny time (n = 158 [36%] nd n = 134 [35%], respectively). Bortezomib ws most commonly dministered in doublet regimen of bortezomib plus dexmethsone (61% of IV nd 49% of SC ptients). Overll, 38% of IV nd 50% of SC ptients received triplet regimens, most commonly bortezomib-lenlidomide-dexmethsone (25% nd 27%, respectively), nd bortezomib-cyclophosphmide-dexmethsone (7% nd 17%, respectively). Only ~1% of ptients in ech group received qudruplet regimens (including bortezomib-cyclophosphmide-lenlidomide-dexmethsone nd bortezomib-cyclophosphmide-dexmethsone+pegylted liposoml doxorubicin). Similr initil doses of bortezomib were observed with both routes of dministrtion t medins of 1.29 mg/m 2 (rnge, ) in the IV group nd 1.30 mg/m 2 (rnge, ) in the SC group (P = ). Medin durtions of tretment were 116 dys (rnge, ) in the IV group nd 142 dys (rnge, ) in the SC group (P = 0.019). At the 16-week time point, 97 of 815 ptients hd required bortezomib dose reductions; greter number of ptients required dose reductions in the IV group (57 of 436 ptients [13%]) thn in the SC group (40 of 379 ptients [11%]). A similr pttern of more frequent dose reductions in the IV group thn the SC group ws observed t the 24- nd 32-week time points: 66 of 436 ptients (15%) nd 45 of 379 ptients (12%) in the IV group nd SC group, respectively, required dose reductions t 24 weeks, nd 69 of 436 ptients (16%) nd 49 of 379 ptients (13%) in the IV group nd SC group, respectively, required dose reductions t 32 weeks. At the 16-week time point, the most common dose reductions (bsed on djusted first dose nd subsequent dose dt) were from 1.3 to 1.0 mg/m 2. Among ptients who hd dose reduction t 16 weeks, the medin time to dose reduction ws numericlly shorter in the IV group (49 dys [rnge, 7 112]) thn in the SC group (56 dys [rnge, 3 105]; men [stndrd devition], 50.2 [27.6] dys vs 53.4 [29.4] dys for the IV nd SC groups, respectively; P = 0.30). Among ptients who hd dose reduction by 24 or 32 weeks, the medin times to dose reduction were similr between the two groups (24 weeks: 56 dys [rnge, 7 161] nd 56 dys [rnge, 3 161] in the IV nd SC groups, respectively; 32 weeks: 62 dys [rnge, 7 203] nd 63 dys [rnge, 3 217] in the IV nd SC groups, respectively). Across the whole per-protocol popultion, medin time to dose reduction ws not reched; however, lthough the difference ws not sttisticlly significnt, the overll trend suggests ptients receiving IV bortezomib re more likely to require dose reduction thn those receiving SC bortezomib (Figure 2). In the univrite regression nlysis using the Cox proportionl hzrds model, no vrible ws ssocited with time to dose reduction t 16, 24, nd 32 weeks. In the multivrite nlysis, initil bortezomib dose ws identified s the only sttisticlly significnt covrite of time to dose reduction t 16 weeks (hzrd rtio [HR], [95% confidence intervl (CI), ]; P = ); t 24 weeks (HR, (95% CI, ); P = ), nd t 32 weeks (HR, (95% CI, ); P = ). Dt on resons for tretment discontinution were vilble for 311 ptients, including 161 ptients in the IV group nd 150 ptients in the SC group. Among these ptients, the most common resons for tretment discontinution in the IV nd SC groups included tretment completion (79 ptients [49%] nd 63 ptients [42%], respectively); progression or relpse (20 ptients [12%] nd 23 ptients [15%], respectively); toxicity (mediclly required; 23 ptients [14%] nd 20 ptients [13%], respectively); nd ptient-specific resons (15 ptients [9%] nd 15 ptients [10%], respectively). After medin follow-up time of 29.9 months (rnge, ) in the IV group nd of 22.4 months (rnge, ) in the SC group (P < ), the medin OS ws not reched (Figure 3). However, OS prospects remined similr in the IV nd SC groups, with 1-yer survivl rtes of 84% nd 87%, respectively, nd 2-yer survivl rtes of 78% nd 79%, respectively. discussion The results from this retrospective nlysis of EHR dt in the US community oncology setting indicte tht SC bortezomib is ssocited with prolonged durtion of tretment, numericlly fewer dose reductions, trend for longer time to dose reduction, nd similr 1-yer nd 2-yer OS rtes compred with IV bortezomib. In ddition, initil bortezomib dose ws identified s the only sttisticlly significnt covrite of time to dose reduction in multivrite nlysis. Together, these findings support our hypothesis tht outcomes ssocited with SC dministrtion of bortezomib re s good s those with IV bortezomib in newly dignosed MM ptients in the clinicl setting nd reflect the results of the phse 3 MMY-3021 study fter prolonged follow-up Journl of Clinicl Pthwys Mrch

5 Tble 1. Ptient Demogrphic nd Clinicl Chrcteristics t Bseline nd Prior to Bortezomib Tretment According to Route of Bortezomib Administrtion (Per-Protocol Popultion) IV (n = 436) SC (n = 379) P-vlue Age, yers Men (SD) Medin (rnge) 66 (12) 67 (34 89) 67 (12) 68 (32 93) Age 65 yers, n (%) 245 (56) 231 (61) Mle, n (%) 243 (56) 206 (54) BMI Men (SD) Medin (rnge) 29.0 (7.3) 27.8 ( ) 28.1 (5.9) 27.2 ( ) BMI 25 kg/m 2, n (%) 297 (68) 253 (67) ISS stge, n (%) I II III Unknown/missing 82 (19) 114 (26) 187 (43) 53 (12) 84 (22) 96 (25) 158 (42) 41 (11) KPSS score, n (%) Unknown/missing 39 (9) 126 (29) 111 (25) 122 (28) 38 (9) 59 (16) 116 (31) 96 (25) 95 (25) 13 (3) MM subtype, n (%) IgA IgG Light chin Other 63 (14) 165 (38) 79 (18) 129 (30) 58 (15) 154 (41) 71 (19) 96 (25) Bseline comorbidities, n (%) Yes No 188 (43) 248 (57) 155 (41) 224 (59) Common bseline comorbidities ( 10% in either group), n (%) Generl b Endocrine/metbolic Crdiovsculr Musculoskeletl Renl/urinry Hemtologic 97 (22) 59 (14) 52 (12) 50 (11) 54 (12) 42 (10) 55 (15) 46 (12) 50 (13) 45 (12) 34 (9) 25 (7) c Pyer sttus, n (%) Medicre Privte Other Unknown/missing 213 (49) 156 (36) 49 (11) 18 (4) 201 (53) 116 (31) 45 (12) 17 (4) IgD, IgM, subtype missing or unknown. b Includes weight loss, norexi, dehydrtion, dirrhe, dyspne, hypervolemi, mlise, nuse, pin, nd sepsis. c Sttisticlly significnt t the.05 level. Abbrevitions: BMI, body mss index; ISS, Interntionl Stging System; KPSS, Krnofsky Performnce Sttus Scle; MM, multiple myelom; SD, stndrd devition. Mrch 2016 Journl of Clinicl Pthwys 39

6 Probbility of Dose Reduction weeks 24 weeks 32 weeks Log-rnk test: P = 0.26 P = 0.09 P = 0.22 IV SC Time to Dose Reduction (weeks) IV(n): SC (n): Figure 2. Kpln-Meier Estimtes of Time to Dose Reduction t 16, 24, nd 32 Weeks (Per-Protocol Popultion) Abbrevitions: IV, intrvenous; SC, subcutneous. Survivl Probbility Log-rnk test: P = Overll Survivl (months) IV (n): SC (n): IV SC Figure 3. Kpln-Meier Estimtes of OS (Per-Protocol Popultion) The number of ptients in the SC group is limited fter 30 months; therefore these dt re not fully mture. Medin followup ws 29.9 months in the IV group nd 22.4 months in the SC group. Abbrevitions: IV, intrvenous; OS, overll survivl; SC, subcutneous. Notbly, the prolonged tretment durtion with SC versus IV dministrtion (142 vs 116 dys), considered together with the similr medin bortezomib dose per month (5.3 nd 5.5 mg/m 2 in the SC nd IV groups, respectively), suggests potentilly cliniclly significnt, higher overll cumultive dose of bortezomib with SC dministrtion nd better tretment outcomes. In reltion to this, n nlysis of dt on bortezomib-melphln-prednisone from the phse 3 VELCADE s Initil Stndrd Therpy in Multiple Myelom: Assessment with Melphln nd Prednisone (VIS- TA) tril 25 hs shown tht higher cumultive bortezomib dose (due to prolonged tretment durtion nd/or dose intensity) is ssocited with improved survivl. Prolonged follow-up is required to determine whether the dt from this study in community oncology setting my support these findings from VISTA. This point hs become incresingly importnt s MM is incresingly being considered continuous therpy disese; rndomized studies 26 nd met-nlysis 27 hve reported benefits from mintennce or continuous therpy with novel gents such s bortezomib, lenlidomide, nd thlidomide, in terms of incresed response rte, PFS, nd OS. Indeed, s these community clinicl prctice dt continue to mture, further nlyses will be required to evlute the impct of bortezomib dministrtion route on OS s well s other tretment outcomes such s PFS, time to tretment filure, nd time to next therpy. Nevertheless, in the context of the similr efficcy seen in previous studies with both routes of bortezomib dministrtion, 6-18 use of SC versus IV bortezomib my be importnt in terms of mintining ptients on ctive therpy for longer. Two survey studies hve demonstrted tht mjority of ptients prefer SC over IV bortezomib, 20,21 nd one of these studies highlighted other potentil contributory fctors of improved ptient convenience nd reduced ptient burden with SC dministrtion, s evidenced by reductions in chir time nd infusion center visit time compred with IV bortezomib. 21 Although SC dministrtion of bortezomib hs been ssocited with injection-site rections in number of studies nd reports, 6,11,21,28,29 including the originl phse 3 study, 3,4 these hve typiclly been only mild to moderte in severity nd hve generlly resolved rpidly. 4,6,11,29 Notbly, the incidence nd severity of such rections my be improved through optimizing SC dministrtion techniques to further enhnce the tolerbility of this route of dministrtion. 7,20,30 This study hs severl limittions. Dt were collected for clinicl nd not reserch purposes; thus, ssocitions, but not cuslity, cn be detected. Ptients nd physicins re heterogeneous; therefore, demogrphics nd prctice behviors my differ between clinics. Dt collection my not be s complete cross the entire popultion. Missing vlues my result in exclusion from the study or nlysis. Ptient tretment history outside the USON my not be fully cptured in the ikm EHR. Adverse events re not grded in the ikm EHR. The USON encourges the use of evidence-bsed tretment guidelines; therefore, results my differ from other community-bsed prctices. In the bsence of rndomiztion, the SC bortezomib cohort, on verge, ppered to hve lower level of generl bseline comorbidities thn the IV bortezomib cohort, lthough the resons for this difference re not cler. Multivrite regressions cnnot fully djust for the differences between the two rms. Additionlly, due to the dte of the US Food nd Drug Administrtion pprovl of SC dministrtion of bortezomib, in Jnury 2012, there ws n symmetric follow-up between ptients receiving IV versus SC bortezomib who were included in this study; thus, there is the possibility tht higher proportion of ptients in the SC group my hve still been receiving bortezomib therpy t the end of the study follow-up period (July 31, 2014), nd 40 Journl of Clinicl Pthwys Mrch

7 so prolonged follow-up period is desirble. The bsence of comorbidity dt does not indicte bsence of the comorbidity; rther, it is the bsence of documenttion of the comorbidity. Although dt-qulity checks were conducted, some vribles of interest were not complete or vilble from the dt source, nd further ptient chrt reviews will be necessry to wrrnt reserch on tretment outcomes in terms of response, PFS, nd sfety, including peripherl neuropthy. As for comorbidities, the bsence of dverseevent dt does not indicte bsence of dverse events. The per-protocol nlysis pproch, excluding ptients who switched routes of dministrtion during tretment, my potentilly hve confounded the investigtion of the true tolerbility of ech route of dministrtion. Notbly, there ws substntilly higher number of ptients who switched from IV to SC dministrtion (n = 216) thn who switched from SC to IV dministrtion (n = 27). Given the demonstrted improvement in the systemic sfety profile of bortezomib with SC versus IV dministrtion in the phse 3 MMY-3021 study,3,4 these switchers from IV to SC dministrtion my hve comprised those ptients who were not tolerting IV bortezomib s well. As result, there my hve been selection bis for the per-protocol popultion used for these nlyses towrds those who better tolerted IV bortezomib. Additionlly, the imblnce between the IV nd SC groups in terms of use of doublet or triplet regimens my lso hve ffected the rte of dose reductions; higher proportion of ptients in the SC group received triplet therpy, which, compred with doublet therpy, my hve required dditionl dose reductions due to the dded toxicity profile of third gent. conclusion Our findings suggest similr tretment outcomes nd n overll trend for prolonged tretment nd fewer dose reductions with SC bortezomib compred with IV bortezomib s initil therpy in previously untreted MM ptients in the community oncology setting. Overll, these findings suggest similr tretment outcomes nd the potentil for improved tolerbility with SC versus IV bortezomib s initil therpy in routine clinicl prctice. REFERENCES 1. Velcde (bortezomib) for injection [product chrcteristics]. Beerse, Belgium: Jnssen-Cilg Interntionl NV; document_librry/epar_-_product_informtion/humn/000539/wc pdf. 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