Multiple Myeloma: Approach to the Elderly

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1 Multiple Myeloma: Approach to the Elderly Peter Anglin MD, FRCPC, MBA Stronach Regional Cancer Centre Newmarket, ON PMH Myeloma Day May 12, 2017

2 Peter Anglin MD Disclosures Speakers Bureau Advisory Boards Celgene Celgene, Janssen

3 Overview Myeloma and the Elderly Myeloma and age context Age and Frailty Assessment Therapy Front line Rd front line FIRST data Relapsed myeloma Doublets vs Triplets

4 To assess the overall health status of my MM patients > 65 years I use the following: 1) Age alone 2) Age, performance status and clinical judgement considering all comorbidities 3) The IMWG Frailty Score 4) A geriatric assessment tool other than the IMWG Score. 5) The time it takes a patient to move form the clinic waiting room is directly proportional to their unfitness

5 A 79 yo woman with standard risk MM lives 20 minutes from hospital. She has average comorbidities for her age. Your initial recommendation for treatment is: 1) Bortezomib, melphalan, prednisone (BMP) 2) Cyclophosphamide, melphalan, prednisone (CyBorD) 3) Thalidomide, melphalan, prednisone (MPT) 4) Melphalan, prednisone (MP) 5) Lenalidomide, dexamethasone (Rd)

6 Today s practical working definition of elderly 65 years or older Non-transplant eligible Distinction between fit and frail elderly Will focus on the 75+ patient to some degree

7 J Natl Cancer Inst. 2014;106(5) Based on Surveillance Epidemiology and End Results database. Myeloma is a disease of the elderly Age-specific (crude) incidence of multiple myeloma

8 Gains in survival in MM have benefitted young > older up to recently. Five-year relative survival by patient age and chronological year at diagnosis. Based on Surveillance Epidemiology and End Results survival of multiple myeloma patients. Pulte D, Gondos A, Brenner H. Improvement in survival of older adults with multiple myeloma: results of an updated period analysis of SEER data. Oncologist. 2011;16(11):

9 The use of novel agents are now showing benefits for survival in older patients. Survival of 107 unselected NTE patients from a community setting. Hematol Oncol Dec;34(4): doi: /hon Epub 2015 Apr 21

10 Treatment choice is a synthesis of many factors more so in the elderly

11 Assessing Frailty Arbitrary definitions in past > 75 years? Inadequate treatment of fit patients Overtreatment of frail patients Currently most clinicians use: chronologic age performance status Does not account for heterogeneity clinician judgment of elderly population Geriatric impairments are highly prevalent in elderly patients (even in those with good performance status) may not be easily detected may impact a patient s ability to complete treatment Hamaker ME, Prins MC, Stauder R: The relevance of a geriatric assessment for elderly patients with a haematological malignancy: A systematic review.leuk Res 38: , 2014

12 Frailty Assessments in Myeloma: The IMWG Frailty Score First frailty index specific for myeloma Based on: Age(3 groups) ADL (6 self-care tasks) IADL (8 household tasks) Charlson co-morbidity Index (18 factors) Defines 3 groups: 0 = fit 1 = intermediate-fit 2 = frail IMWG Frailty Scale 1 Age Score 75 yrs yrs 1 > 80 yrs 2 Activity of Daily Living score > Instrumental Activity of Daily Living score > Charlson Comorbidity Index score Total Points 1 Palumbo A, et al. Blood 2015; 125:

Analysis Unfit vs Fit, HR=1.61 p=0.042 Frail vs Fit, HR=3.57 p<0.

13 IWMG Frailty Score: Fit vs. Unfit vs. Frail Overall Survival 39% 31% Patients (%) 1-yr OS Fit 96% Unfit 93% Frail 78% 30% Multivariate Analysis Unfit vs Fit, HR=1.61 p=0.042 Frail vs Fit, HR=3.57 p<0.001 Lower risk Death FIT ISS 1-2 FISH neg Higher risk Death FRAIL ISS 3 FISH pos Fit defined as: score=0 Unfit defined as: score=1 Frail defined as: score>2 Slide courtesy of Palumbo, ASH 2013

14 Slide courtesy of Palumbo, ASH 2013

Real-World Prospective Evaluation of Different Geriatric Assessment Tools in Unselected Elderly Patients with Symptomatic Myeloma Dimopoulos et al, Blood 2015 126:4242 120 consecutive patients Dx MM

15 Real-World Prospective Evaluation of Different Geriatric Assessment Tools in Unselected Elderly Patients with Symptomatic Myeloma Dimopoulos et al, Blood : consecutive patients Dx MM at a single centre Median age 76 (66-92) ISS stage: I: 26% II: 24% III: 50% High risk cytogentics: 19% egfr < 30 ml: 22% Therapy: ImID based: 47%, PI based: 53% IMWG Frailty Score: Fit: 29% 39% Unfit: 17% cf IMWG 31% Frail: 54% 30% Was not prognostic for OS

16 Frailty Assessments in Myeloma IMWG Frailty Score 1 Revised Myeloma Co-morbidity Index 2 Mayo Frailty System 3 N (172 no ASCT) Median age 74 (46% 75) 63 (13% 75) 65 (33% 70) Population 6 study regimens Variable Len-based 63% BTZ-based 22% ASCT 39% Factors Access Age ADL IADL CCI frailtyscorecalculator.net/ 1 Palumbo A, et al. Blood 2015; 125: ; 2 Engelhardt M, et al. Haematologica Feb 2017 [Epub ahead of print], 3 Milani P, et al. Am J Hematol 2016: Renal (Calc GFR) Lung (PFTs) KPS Fragility Age Cytogenetics ex.org Age 70 ECOG PS 2 NT-ProBNP 300 ng/l

17 Overall survival according to NT-ProBNP > 300 ng/l Am. J. Hematol. 91: , 2016

18 Overall Survival According to the Frailty System Based on Age 70, ECOG-PS 2, and NT-proBNP 300 ng/l P <.0001 Am. J. Hematol. 91: , 2016

19 Canadian MM Alogrithm recent past: Focus on non-transplant years and fit > years and/or frail CyBorD + ASCT [+/- Lenalidomide maintenance] Chemotherapy [VMP; CyBorD; Lenalidomide + dex on clinical trial]! Second ASCT if months from first Progression Second-line therapy (Lenalidomide + dex- or bortezomib-based) Third-line therapy (Bortezomib- or IMiD-based; cyclophosphamide often included (i.e.,rcd); or clinical trial) Double refractory * (Pomalidomide + dex, often with 3 rd agent, i.e., PCd or PVD; or clinical trial) Palliation/Death *To lenalidomide and bortezomib!

20 The VISTA trial set the bar for initial therapy for non-transplant eligible patients became the standard for initial therapy in many places including Ontario. Median age: 71 years San Miguel J F et al. JCO 2013;31:

Pneumonia 7% 5% Hypokalemia 7% 3% Asthenia 6% 3% Discontinuation due to AE 15% 14% AEs were higher with Bort/Mel/Pred vs.

21 VISTA: Adverse Events Grade 3/4 AEs Bort/Mel/Pred 5% Pts 35 (n=340) MP (n=337) Neutropenia 40% 38% Thrombocytopenia 38% 31% Anemia 19% 28% Leukopenia 24% 20% Lymphopenia 20% 11% Peripheral sensory neuropathy *13% (44% all grades) 0% Neuralgia 9% <1% Fatigue 8% 2% Diarrhea 8% 1% Pneumonia 7% 5% Hypokalemia 7% 3% Asthenia 6% 3% Discontinuation due to AE 15% 14% AEs were higher with Bort/Mel/Pred vs. MP during cycles 1-4, but similar during cycles San Miguel JF, et al. J Clin Oncol. 2013;31:448-55; Mateos et al. J Clin Oncol. 2010;28:p

Initial Therapy in Older Adults With MM: Randomized Trials of MP With or Without the Addition of Novel Agents Trial Name Reference Regimen Median PFS (months) Median OS (months) Italian Group for

22 Initial Therapy in Older Adults With MM: Randomized Trials of MP With or Without the Addition of Novel Agents Trial Name Reference Regimen Median PFS (months) Median OS (months) Italian Group for Hematological Palumbo et al 15 MP Malignancies of the Adult (GIMEMA) MPT Intergroupe Francophone du Myelome Facon et al 16 MP (IFM) MPT Hemato-Oncologie voor Volwassenen Wijermans et al 17 MP 9 31 Nederland (HOVON) 49 MPT Intergroupe Francophone du Myelome Hulin et al 20 MP (IFM) MPT Eastern Cooperative Oncology Group Rajkumar et al 19 Rd (at 2 years) (ECOG) E4A03 RD (at 2 years) Multiple Myeloma 015 (MM015) Palumbo et al 18 MP (at 3 years) MPR (at 3 years) MPR-R (at 3 years) Velcade As Initial Standard Therapy in Multiple Myeloma (VISTA) trial San Miguel et MP al 21 MPV * Discontinuation rate because of toxicity, specifically during induction where applicable. Global (ie, any or nonhematologic ) toxicity incidence not reported. Statistically significant for MPR-R v MP and MPR-R v MPR only. Wildes T M et al. JCO 2014;32:

23 Community-Based Phase 3B UPFRONT Trial J Clin Oncol Nov 20;33(33):

24 The UPFRONT Trial showed little difference between 3 bortezomib regimens and reflected real world experience J Clin Oncol Nov 20;33(33):

25 UPFRONT: Selected adverse events

26 Survival with Bortezomib-containing Regimens in Non-transplant Eligible Patients:Canadian Experience 113 consecutive NTE patients 1 Overall Survival 1 Progression-free Survival Cumulative survival Bort/Mel/Pred CyBorD Bort/Dex Cumulative survival Bort/Mel/Pred CyBorD Bort/Dex Months since treatment started Months since treatment started 27. Jimenez-Zepeda et al. 57 th Annual ASH Meeting; 2015 Dec 5-8 [Abstract 1846].

27 Selected Studies in Newly Dx Elderly Patients With Myeloma # Patients age > 80 years: 41% in VP, 27% in VCP, and 30% in VMP arms. Journal of Clinical Oncology, Vol 34, No 30 (October 20), 2016: pp

FIRST: Trial Design 56 AMT, anti-myeloma therapy; ISS, International Staging System; LEN, lenalidomide; LoDEX, low-dose dexamethasone; LT, long-term; MEL, melphalan; MPT,

dexamethasone until disease progression; Rd18, lenalidomide plus low-dose dexamethasone for 18 cycles; THAL, thalidomide. Facon T, et al.

28 FIRST: Trial Design 56 AMT, anti-myeloma therapy; ISS, International Staging System; LEN, lenalidomide; LoDEX, low-dose dexamethasone; LT, long-term; MEL, melphalan; MPT, melphalan-prednisone-thalidomide; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PRED, prednisone; pt, patient; Rd, lenalidomide + low-dose dexamethasone until disease progression; Rd18, lenalidomide plus low-dose dexamethasone for 18 cycles; THAL, thalidomide. Facon T, et al. FIRST Study: Updated Overall Survival in Stem Cell Transplant-ineligible Newly Diagnosed Multiple Myeloma Patients Treated With Continuous Lenalidomide Plus Low-dose Dexamethasone vs Melphalan, Prednisone, and Thalidomide. ASCO 2015, abstract #8524.

29 FIRST Trial: Patient Enrollment by Country 22 A total of 4 continents from 18 countries Facon T, et al. Blood. 2013;122:abstract 2.

30 FIRST - Methods Key eligibility criteria 1 Previously untreated, symptomatic, and measurable MM as defined by IMWG criteria 2 Age 65 years, or if aged < 65 years, not candidates for stem cell transplant ECOG PS 0, 1, or 2 Renal impairment was allowed, but patients requiring dialysis were excluded ECOG PS, Eastern Cooperative Oncology Group performance status; IMWG, International Myeloma Working Group; MM, multiple myeloma. 1. Benboubker L, et al. N Engl J Med. 2014;371: Durie B, et al. Leukemia. 2006; 20:

31 FIRST - Baseline Characteristics Characteristic Rd Continuous (n = 535) Rd18 (n = 541) MPT (n = 547) Median age, yrs (range) 73 (44-91) 73 (40-89) 73 (51-92) > 75 yrs, % Male, % ECOG PS score 0/1/2, % 29/48/22 30/49/21 29/50/20 ISS III, % CrCl < 30 ml/min, % High-risk cytogenetics, % a a Complete cytogenetics profile for 762 patients (248 in Rd continuous, 261 in Rd18, and 253 in MPT); high-risk cytogenetics included t(4;14), t(14;16), and del(17p). CrCl, creatinine clearance; del, deletion; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; MPT, melphalan, prednisone, thalidomide; Rd continuous, lenalidomide plus low-dose dexamethasone until disease progression; Rd18, lenalidomide plus low-dose dexamethasone for 18 cycles; t, translocation. Benboubker L, et al. N Engl J Med. 2014;371:

32 FIRST: Final Progression-free Survival Survival probability Len/Dex to Progression Len/Dex18 MPT 4-year PFS 32.6% Median PFS, mos year PFS, % HR (95% CI) Len/Dex to Progression vs. MPT: 0.69 ( ), p< % 14.3% Progression-free survival (months) Facon et al. 58 th Annual ASH Meeting; 2016 Dec 3-6 [Abstract 241].

33 FIRST: Updated Overall Survival Survival probability % 4-year OS 59.0% 58.0% Len/Dex to Progression Len/Dex18 MPT Median OS, mos year OS, % HR (95% CI) Len/Dex to Progression vs. MPT: 0.78 ( ), p= Overall survival (months) CI: confidence interval; HR: hazard ratio; Len/Dex: lenalidomide and low-dose dexamethasone until disease progression; Len/Dex18: lenalidomide and low-dose dexamethasone for 18 cycles; MPT: melphalan, prednisone and thalidomide; OS: overall survival. 29. Facon et al. 58 th Annual ASH Meeting; 2016 Dec 3-6 [Abstract 241]. 33

34 FIRST: Effect of Subgroup on Progression-Free Survival PFS favored Rd continuous over MPT in the majority of subgroups analyzed Subgroup ITT population Age > 75 yrs Age 75 yrs ISS stage: I or II ISS stage: III CrCl < 30 ml/min 30 CrCl < 50 ml/min 50 CrCl < 80 ml/min CrCl 80 ml/min ECOG PS 0 ECOG PS 1 ECOG PS 2 Lactate dehydrogenase < 200 U/L Lactate dehydrogenase 200 U/L High risk b Non-high risk b Favours Rd Rd Cont a MPT a HR (95% CI) 343/ / (0.59, 0.79) 124/ / (0.60, 0.99) 219/ / (0.54, 0.77) 201/ / (0.55, 0.81) 142/ / (0.57, 0.90) 29/45 40/ (0.57, 1.51) 83/126 91/ (0.47, 0.85) 158/ / (0.55, 0.87) 73/123 98/ (0.49, 0.91) 86/ / (0.37, 0.66) 171/ / (0.62, 0.94) 84/119 82/ (0.60, 1.11) 282/ / (0.55, 0.77) 60/86 77/ (0.70, 1.38) 39/43 37/ (0.81, 2.01) 125/ / (0.52, 0.84) a Number of events/number of patients. b Complete cytogenetics profile for 501 patients (248 in Rd continuous and 253 in MPT); high-risk cytogenetics included t(4;14), t(14;16), and del(17p).

35 PFS in FIRST According to Age A Age 75 years Median (months) 4-year (%) Rd to Progression Rd MPT HR (95% CI) Rd to Progression vs. MPT: 0.64 (0.53 to 0.77) Rd to Progression vs. Rd18: 0.68 (0.56 to 0.82) Rd18 vs MPT: 0.97 (0.81 to 1.15) B *Age >75 years Median (months) 4-year (%) Rd to Progression Rd MPT HR (95% CI) Rd to Progression vs. MPT: 0.80 (0.62 to 1.03) Rd to Progression vs. Rd18: 0.78 (0.61 to 1.01) Rd18 vs MPT: 1.03 (0.80 to 1.33) Patients (%) Patients (%) Progression-Free Survival (months) Progression-Free Survival (months) Safety REVLIMID plus low-dose dexamethasone was generally well tolerated in the Rd to Progression and Rd18 arms, with similar safety profiles (rates of grade 3 to 4 treatment-emergent adverse events [TEAEs]) in patients 75 years or >75 years). 4

36 FIRST: Grade 3 / 4 Adverse Events Selected Grade 3/4 Adverse Events, % a Hematologic Rd Continuous n = 532 Rd18 n = 540 MPT n = 541 Neutropenia Anemia Thrombocytopenia Febrile neutropenia Non-hematologic Infections Pneumonia Cataract Deep vein thrombosis Diarrhea Pulmonary embolism Constipation Peripheral sensory neuropathy 1 < 1 9

37 FIRST: SPM 65 SPM, n (%) Rd Continuous (n = 532) Rd18 (n = 540) MPT (n = 541) Any, n (%) 45 (8.5) 50 (9.3) 54 (10.0) Invasive, n (%) Hematologic Solid tumor 21 (3.9) 3 (0.6) 18 (3.4) 33 (6.1) 2 (0.4) 32 (5.9) 30 (5.5) 12 (2.2) 18 (3.3) Noninvasive (NMSC), n (%) 27 (5.1) 20 (3.7) 26 (4.8) There was a low frequency of pts with hematologic SPMs (AML/MDS) in the Rd continuous and Rd18 arms with no B-cell malignancies Of the 149 pts who experienced SPMs, 90 remain alive AML, acute myeloid leukemia; MDS, myelodysplastic syndromes; MPT, melphalan-prednisone-thalidomide; NMSC, nonmelanoma skin cancer; pt, patient; Rd, lenalidomide + low-dose dexamethasone until disease progression; Rd18, lenalidomide plus low-dose dexamethasone for 18 cycles; SPM, second primary malignancy. Facon T, et al. FIRST Study: Updated Overall Survival in Stem Cell Transplant-ineligible Newly Diagnosed Multiple Myeloma Patients Treated With Continuous Lenalidomide Plus Low-dose Dexamethasone vs Melphalan, Prednisone, and Thalidomide. ASCO 2015, abstract #8524..

38 FIRST (MM-020): Frailty Analysis Frailty Algorithm Source Reference 12: Slide sorter deck: MM-020 Frailty Analysis (Facon) Abstract ASH 2015: Slide 2 IMWG Frailty Scale 1 Proxy for MM-020 Analysis Score Age Age 75 yrs Pts were categorized into 3 severity groups 75 yrsas described by a proxy algorithm based 0 on the IMWG frailty scale yrs yrs 1 > 80 yrs > 80 yrs 2 Activity of Daily Living score EQ-5D: Self Care score > 4 1 (no problem) (moderate or severe problem) 1 Instrumental Activity of Daily Living score EQ-5D: Usual Activities score > 5 1 (no problem) (moderate or severe problem) 1 Charlson Comorbidity Index score Charlson Comorbidity Index score Palumbo A, et al. Blood. 2015;125: IMWG, International Myeloma Working Group; pt, patient. Facon T, et al. A Frailty Scale Predicts Outcomes in Patients With Newly Diagnosed Multiple Myeloma Who Are Ineligible for Transplant Treated With Continuous Lenalidomide Plus Low-Dose Dexamethasone in the FIRST Trial. ASH 2015, abstract #4239. Total 0: Fit 1: Intermediate 2: Frail

39 Impact of Frailty OS by Severity Group for (A) All Tx Arms and for Rd Continuous vs MPT for (B) Fit, (C) Intermediate and (D) Frail Patients 39

40 FIRST: Time to Next Treatment is substantially prolonged by Rd continuous therapy Rd continuous extended the median TTNT compared with MPT Median TTNT was also longer in patients who achieved CR/VGPR Subgroup Rd continuous vs MPT HR & 95% CI Median TTNT (mos) Rd continuous Rd18 MPT Rd continuous vs MPT HR (95% CI) I T T C R / V G P R ³ P R ( ) ( ) ( ) Favors Rd Continuous Favors MPT

41 FIRST (MM-020): Impact of Cytogenetics Progression-Free Survival 110 cont, continuous; HR, hazard ratio; MPT, melphalan, prednisone, and thalidomide; pt, patient; Rd, lenalidomide plus low-dose dexamethasone; Rd18, Rd for 18 cycles. Avet-Loiseau H, et al. Impact of Cytogenetics on Outcomes of Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated With Continuous Lenalidomide Plus Low-Dose Dexamethasone in the FIRST (MM-020) Trial. ASH 2015, abstract #730.

42 Reflections on Rd as front line therapy for older patients Oral and well tolerated Attention to side effect management and dose reductions will optimize compliance and QOL Can reduce visits to clinic for patients Once every 1-2 months Time to next treatment data is impressive There still remains a role for upfront PI therapy

43 Adapted from Palumbo et al, Blood : Treatment Strategy in Older (Frail) MM Patients : What to choose? Specific Characteristics Treatment (Maintenance) Lack of significant renal failure related to myeloma No aggressive disease Peripheral neuropathy Difficult access to hospital Presence of renal failure Aggressive disease Extramedullary disease Easy access to hospital Lenalidomide Based Bortezomib Based Low dose Lenalidomide 2x/mo Bortezomib s/c

44 Canadian MM Alogrithm recent past: Focus on non-transplant years and fit > years and/or frail CyBorD + ASCT [+/- Lenalidomide maintenance] Chemotherapy [VMP; CyBorD; Lenalidomide + dex on clinical trial]! Second ASCT if months from first Progression Second-line therapy (Lenalidomide + dex- or bortezomib-based) Third-line therapy (Bortezomib- or IMiD-based; cyclophosphamide often included (i.e.,rcd); or clinical trial) Double refractory * (Pomalidomide + dex, often with 3 rd agent, i.e., PCd or PVD; or clinical trial) Palliation/Death *To lenalidomide and bortezomib!

45 Options for patients relapsing following bortezomib-based therapy Lenalidomide + Dexamethasone Well known and tolerated Access to additional drugs has created a variety of triplets Carfilzomib + Rd Ixazomib(oral) + Rd Daratumumab+ Rd Triplets have increased side effects Haematologic Non-haematologic

46 Recent Phase III relapsed MM Trials: Focus on age Patient Characteristic Triplet Arm Median age (years) ASPIRE 17 ELOQUENT-2 18 TOURMALINE- MM1 20 CASTOR 21 POLLUX (31-91) (34-89) Comments 12% > 74 58% > 65 53% > 65 12% > 74 11% > 74 Prior # Rx (median) Len 25 mg, d1-21 Len 25 mg, d1-21 Len 25 mg, d1-21 Dex 40 mg, d1, 8, 15, 22 Cfz Cycles 1-12: d1, 2, 8, 9, 15, and 16 Cycles 13-18: d1, 2, 15, and min infusion * Dex 40 mg, d1, 8, 15, 22 Elo 10 mg/kg IV Cycles 1-2: d1, 8, 15, 22 Cycle 3+: d 1, 15 Infusion time (Cycle 3+ ~1 hour) Dex 40 mg, d 1, 8, 15, 22 Ixa 4 mg d1, 8, 15 Bort 1.3 mg/m 2 SC Cycles 1-8: d1, 4, 8, 11 Dex 20 mg, d1, 2, 4, 5, 8, 9, 11, 12 Dara 16 mg/kg IV Cycles 1-3: d1, 8, 15 Cycles 4-8: d1 Every 4 wks thereafter Infusion time (~ hours) Len 25 mg, d1-21 Dex 40 mg, d1, 8, 15, 22 Dara 16 mg/kg IV Cycles 1-2: d1, 8, 15, 22 Cycles 3-6: d1, 15 Cycles 7+: d1 Infusion time (~ hours) 17. Stewart et al. N Engl J Med. 2015;372:142-52; 18. Lonial et al. N Engl J Med. 2015;373:621-31; 20. Moreau et al. N Engl J Med. 2016;341: ; Palumbo et al. N Engl J Med. 2016;375:754-66; 24. Dimopoulos et al. N Engl J Med. 2016;375:

47 Toxicity/Convenience of Triplet Regimens with Len + Dex in Relapsed/Refractory Myeloma Regimen CFZ ELO 2 IXAZOMIB 3 DARATUMUMAB 4 Neutropenia Thrombocytopeni a Hypertension GI Neuropathy Occasional Dyspnea/cough Infusion reactions DC due to toxicity 15% 17% 8.7% 7% Administration 6x/month IV Q 1-2 weeks IV PO IV q k x 8; q 2 wk x 8; q 4 wk Minimum clinic visits (18 cycles) Adapted from Donna Reece

48 Do I consider a triplet for 1 st relapse in my older MM patient High risk cytogenetics? Oral option makes Ixazomibattractive Is my patient frail or fit Logistics of drug delivery Patient choice What is important to them Common sense

49 Treatment algorithm for elderly MM PATIENT STATUS ASSESSMENT Age (score 0 1 2) Charlson (score 0 1) ADL (score 0 1) IADL (score 0 1) FIT UNFIT FRAIL Additive total score = 0 Additive total score = 1 Additive total score 2 GO-GO MODERATE-GO SLOW-GO Full-dose Reduced-dose Further reduced dose Dose level 0 Dose level -1 Dose level -2 Lenalidomide 25 mg/d 15 mg/d 10 mg/d Bortezomib 1.3 mg/m 2 /wk 1.0 mg/m 2 /wk 1.3 mg/m 2 /2wk Dexamethasone 40 mg/wk 20 mg/wk 10 mg/wk Cyclophosphamide 300 mg/m 2 d 1,8,15 50 mg/d 50 mg/qod Slide courtesy of Palumbo, ASH 2013

50 Maintenance Therapy and the Elderly Continuous therapy allows for ongoing disease control Translates to increased PFS and TNTT In high risk patients continue bortezomib on q2 weekly schedule* Rd up front - continuous

51 Take-aways from today Comprehensive geriatric assessments are evolving but have not become standard practice in MM New tools may evolve Dose reductions and side effect management are critical for elderly patients Watch CrCl! Many patients can have long term disease control without CR Rd is now a treatment option for 1 st line standard risk MM Triplet therapy has more toxicity particularly in frail patients Less toxic treatment allows longer treatment

52 A 79 yo woman with standard risk MM lives 20 minutes from hospital. She has average comorbidities for her age. Your initial recommendation for treatment is: 1) Bortezomib, melphalan, prednisone (BMP) 2) Cyclophosphamide, melphalan, prednisone (CyBorD) 3) Thalidomide, melphalan, prednisone (MPT) 4) Melphalan, prednisone (MP) 5) Lenalidomide, dexamethasone (Rd)

Treatment of elderly multiple myeloma patients

SAMO Interdisciplinary Workshop on Myeloma March 30 th -31 st 2012, Seehotel Hermitage, Lucerne Treatment of elderly multiple myeloma patients Federica Cavallo, MD, PhD Federica Cavallo, MD, PhD Division