Karmanos Cancer Institute

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Presentation transcript:

Karmanos Cancer Institute VRD as Frontline Therapy for Transplant-Eligible Patients with Multiple Myeloma Jeffrey A. Zonder, MD Associate Professor, Oncology and Medicine Karmanos Cancer Institute www.amyloidplanet.com

Objectives Beat Bob www.amyloidplanet.com

Important Questions Are the response rates achieved with VRD and CRd similar? How toxic is each regimen? How convenient is each regimen? How much does each regimen cost? What’s “Plan B?”

The Regimens VRD (q 21d) x 8 VRD (q 28d) x 4 CRd (q 28d) x 8 Richardson, et al Blood 2010 Chari AJ, et al ASH 2011 Jakubowiak, et al Blood 2012 PI IV BTZ 1.3 mg/m2 d 1,4,8,11 d 1,4,11,18 CFZ 36 mg/m2 d 1,2,8,9,15,16 Len 25 mg/d x 14d 25 mg/d x 21d Dex 40 mg/wk x 4 cycles 20 mg/wk x 4 cycles 20 or 40 mg d1,4,11,18

EFFICACY: SIMILAR VRD (q 21d) VRD (q 28d) VRD (EVOLUTION) CRd (q28d) Richardson, et al Blood 2010 Chari AJ, et al ASH 2011 Kumar S, et al Blood 2012 Jakubowiak, et al N (Ph 2) 35 38 42 36 ORR 100% 97% 85% VGPR+ 74% 63% 51% 72% CR 37% 24% (10pts)* 39% OS 97% @ 18 mo N/A 100% @ 1 yr PFS 75% @ 18 mo 100% @ 9 mo 68% @ 1 yr 97% @ 12 mo * 6 of 10 MRD(-) No problems mobilizing stem cells and performing ASCT with either VRD or CRd

What do the Experts Say? NCCN (Version 2.2014) mSMART (Version 2013)1 RVD “preferred regimen” for ASCT-eligible pts CRd mentioned but not in “preferred column” Both based on level 2A evidence Neither mentioned for non-ASCT pts mSMART (Version 2013)1 VRd for high-risk ASCT or non-ASCT pts CRd not currently recommended for any pt grp 1. Mikhael JR, et al. Mayo Clin Proc 2013;88(4):360-76

What Would Jesus Do? He’d pick CRd if it could be proved that it increased rate of MRD(-) CR http://bloodjournal.hematologylibrary.org/content/early/2014/03/19/blood-2014-01-550020.full.pdf+html

MRD Testing No standardized methodology thus far Multiparametric flow cytometry (IMF/EuroFlow) Deep sequencing (LymphoSIGHT) Allele-specific PCR Variable concordance and sensitivity ~85% concordance between techniques1 2-log intra-center differences in sensitivity2 Too early to declare CRd the “winner” 1. http://bloodjournal.hematologylibrary.org/content/early/2014/03/19/blood-2014-01-550020.full.pdf+html 2. Flanders A, et al. Blood. 2013;122(6): 1088-1089

Presented by O Landgren in Kyoto, Japan at the 2013 International Myeloma Workshop

TOXICITY: “Less Neuropathy” RVD (q 21d) CRd (q 28d) VTD (sq BTZ; Thal100 mg/d) Richardson, et al Blood 2010 Jakubowiak, et al Blood 2012 Lok A., et al Haematologica 2014 Any Gr 3+ N/A 48% 37% Any PN 80% 23% 24% Gr 3-4 PN 2% 0% 4% Gr 3-4 ANC 9% 17% Gr 3-4 PLT 6% Any DVT 11% PI Dose  44% 19% Dex Dose  31%

“You say Tomato….” In actual practice, “VRD” not standard Bortezomib often adjusted for tolerability Research to Practice ASH Friday Satellite Symposium, New Orleans, LA. December 6th, 2013

CONVENIENCE goes to VRD VRD (q 21d) x 8 CRd (q 28d) x 8 Richardson, et al Blood 2010 Jakubowiak, et al Blood 2012 Weeks of Rx 24 32 PI 32 doses 48 doses Len 112 days 168 days Dex 960 total mg (Unless on S0777: 1280mg) (Thanks, Bob!)

Dollars and Sense VRD:~$66K/six 21-day cycles (~$88K/8 cycles)1 $11K/cycle: $5.5K each for LEN and BTZ/cycle Estimating cost of CRd 28-day cycles CFZ costs $10K/cycle2 (IF you use standard dose!) 1.5 times as much LEN/cycle = ~$8K/cycle $18K/cycle x 8 cycles = $144K Excess cost of CRd for 10K NDMM pts? $560M 1. Kumar S, et al. ASH 2013, abstract 3178. 2. http://www.ascopost.com/issues/september-1-2012/carfilzomib-new-drug-with-accelerated-approval-for-multiple-myeloma.aspx

Sound Familiar? http://www.slate.com/content/dam/slate/archive/2011/04/1_123125_123037_2279927_2290351_110405_sn_rodriguez_tn.jpg.CROP.original-original.jpg

What’s “Plan B?” 2nd PFS CFZ approval based in part on efficacy after prior BTZ-containing therapy No evidence that BTZ can be used after CFZ

Conclusions VRD has ~100% ORR, is more cost effective, and more convenient Neurotoxicity of VRD can be reduced with subQ and/or weekly BTZ dosing Neither regimen has yet been proven in a randomized Phase 3 study S0777: Rd vs VRd (Closed) E1A11: VRd vs CRd (Active) Farber/IFM: VRd +/- Early ASCT (Active)