Clinical Case- Myeloma patient with

early Relapse after ASCT

Edvan de Queiroz Crusoe MD, MSc, PhD

➢ J.P. 60yo, male, mullato

➢ Back pain in the last 4 months, hypertension > 5y

➢ Hb- 9.8g/dL + Cr-2.1mg/dL , Ionic Calcium- 1.31(abnormal)

➢ More than five (5) bones with litic lesion

➢ B2M -9.52, Immunofixation– Lambda and IgG Lambda?,

➢ IgG-332, IgA-16 e IgM-27

➢ Free Light Chains- K=0,1, L=220, R-0.0005 (reverse R- 2200)

➢BM Bx = 30% of plasma cell

October- 2014

MM Lambda- DS-IIIB, ISS-3

UPEPSPEPMspike-0.7g/dl Total- 1.6g/24h

Gamma – 900mg

MM Lambda- DS-IIIB, ISS-3Case 1-

Current Considerations for Initial Treatment of

MM in Younger Pts

• 3- drugs induction followed by ASCT[1]

• Maintenance therapy post autologous transplantation[2]

• Maximize duration of first response[3,4]

• Assessing depth of response and understanding implications for patient outcome[5]

1. Cavo M, et al. Lancet. 2010;376:2075-2085. 2. McCarthy PL, et al. Expert Rev Hematol. 2014;7:55-66. 3. Palumbo A, et al. N Engl J Med. 2011;364:1046-1060. 4. Lenhers N, et al. ASH 2013. Abstract 3183. 5. Paiva B, et al. Blood. 2012;119:687-691.

Moreau P, et al. Blood. 2016;127:2569-2574.

Phase III IFM 2013-04 Trial: Efficacy Outcomes

• Significantly higher rates of VGPR (primary endpoint) and PR with 4 cycles VTD vs VCD induction therapy

• In per protocol analysis, trend toward significantly higher numbers of CD34+ cells harvested for ASCT with VTD vs VCD (P = .05)

• Hematologic AEs greater in VCD arm; higher rates of peripheral neuropathy in VTD arm.

Response,*† % VTD (n = 169)

VCD (n = 169)

P Value

≥ CR 13.0 8.9 .22

≥ VGPR 66.3 56.2 .05

≥ PR 92.3 83.4 .01

*Centralized assessment by IMWG criteria 2011. †Intent-to-treat analysis.

➢ VCD x 5 + pamidronate+ ASCT x 1

➢ sCR- FLC Ratio=1.76

No Maintenance

Case 1-

Feb 2016- 8 months after ASCT

➢ No Anemia, normal calcium

➢urinary Protein 24h= 3,5g/24h, Cr- 2mg/dL

➢ rFLC= 0.003, dFLC-365 ,

➢ Renal Biopsy - No amiloide

➢ B2M- 6

➢ FISH t(4;14) MM Lambda, R-ISS-3uPEP

Case 1-

Dean Smith, et al.

➢ Progression events were more common in the context of t(14;16) and t(4;14). ➢ All patients with t(14;16) and 82% witht (4;14) had an additional genetic lesion.

16% developed new FISH abnormalyties; Most commom 13q -(43,1%), followed by 1q+ (41,4%)

Phase III Lenalidomide-Based Treatment Options for R/R Myeloma

Trial ORR, % ≥ CR, % ≥ VGPR, % Median PFS, Mos

Median OS, Mos

Median F/u (OS), Mos

ASPIRE: KRd vs Rd[1,2]

87 vs 67 32 vs 9 70 vs 4026.3 vs 17.6

HR: 0.6948 vs 40HR: 0.79

67

TOURMALINE-MM1:IxaRd vs Rd[3]

78 vs 72 14 vs 7 48 vs 3920.6 vs 14.7

HR: 0.74NR 23.0

POLLUX: DRd vs Rd[4,5]

93 vs 76 46 vs 20 78 vs 45NR vs 17.5HR: 0.44

NR vs NRHR: 0.63

32.9

ELOQUENT-2: ERd vs Rd[6,7]

79 vs 66 5 vs 9 35 vs 2919.4 vs 14.9

HR: 0.7348.3 vs 39.6

HR: 0.7848.0

1. Stewart AK, et al. N Engl J Med. 2015;372:142-152. 2. Stewart AK, et al ASH 2017 Abstract 743, 3-Moreau P, et al. N Engl J Med. 2016;374:1621-1634. 4. Dimopoulos M, et al. N Engl J Med. 2016;375:1319-1331. 5. Dimopoulos M, et al. ASH 2017. Abstract 739. 6. Lonial S, et al. N Engl J Med. 2015;373:621-631. 7. Dimopoulos MA, et al. EHA 2017. Abstract S456.

Trial ORR, % ≥ CR, % ≥ VGPR, % Median PFS, Mos

Median OS, Mos

Median F/u (OS), Mos

ENDEAVOR: Kd vs Vd[1,2]

77 vs 63 13 vs 6 54 vs 2918.7 vs 9.4HR: 0.53

47.6 vs 40 HR: 0.79

37.0

CASTOR:DVd vs Vd[3,4,5]

84 vs 63 26 vs 10 62 vs 2916.7 vs 7.1HR: 0.33

NRHR 0.63

26.9

PANORAMA-1:PanoVd vs Vd[6,7]

61 vs 55 11 vs 6 28 vs 1612.0 vs 8.1HR: 0.63

40 vs 36HR: 0.94

---

Elotuzumab(Phase II):EVd vs Vd[7]

66 vs 63 4 vs 4 36 vs 279.7 vs 6.9HR: 0.72

NRHR: 0.61

16.0

Phase III Bortezomib-Based Treatment Options for R/R Myeloma

1. Dimopoulos MA, et al. Lancet Oncol. 2016;17:27-38. 2. 2- Dimopoulos et al. IMWS india 2017, 3- Palumbo A, et al. N Engl J Med. 2016;375:754-766. 4. Lentzsch S. ASH 2017. Abstract 1852. 5. Mateos MV, et al. ASH 2016. Abstract 1150. 6. San-Miguel JF, et al. Lancet Oncol. 2014;15:1195-1206. 7. San-Miguel JF, et al. ASH 2015. Abstract 3026. 8. Jakubowiak A, et al. Blood. 2016;127:2833-2840.

Which options at first relapse?

1-VTd/VRd

2- Kd

3- KRd

4- DVd

5- DRd

Feb 2016- 8 months after ASCT

KRd x 14- VGPR! Urinary protein 24h= 230mg/24h

rFLC= 0.10 Cr- 1.2mg/dL, Immunoparesis

July 2017- urinary Prot. 24h- 1.1g/24h!!!! IgG-270, (IgA y IgM) ↓Cr-1.8mg/dL,dFLC 1250, rFLC 0.001 Hb-10.2g/dL,

4% of plasma cell in peripheral blood.

Feb 2016-

Which options at second relapse?

1- KPd

2- DRd

3- DVd

4- DPd

5- Clínical trial

6- Pray

July 2017-

Feb 2018-

DRd x 3, DPd x 2- VGPR! Urinary protein 24h= 455mg/24h

rFLC= 0.15 Cr- 1.6mg/dL,

Peripheral plasma cell- negative

Obrigado!

edvancrusoe@gmail.com

Thank You!