1. Phase III MAIA: Daratumumab + Len/Dex vs Len/Dex in Transplantation-Ineligible Newly Diagnosed Multiple Myeloma
Integrating New Malignant Hematology Findings Into Practice: Independent Conference Coverage of ASH 2018* December 1-4, 2018; San Diego, California
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
Dex, dexamethasone; Len, lenalidomide.
Supported by educational grants from AbbVie, AstraZeneca, Celgene Corporation, Dova Pharmaceuticals, Incyte, Jazz Pharmaceuticals, Novartis Pharmaceuticals, Pharmacyclics, Seattle Genetics, and Takeda Oncology.

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3. Daratumumab, Lenalidomide, and Dexamethasone in Myeloma: Background
Continuous Rd or triplet VRd followed by maintenance is considered standard of care for ASCT-ineligible newly diagnosed MM
Phase III FIRST trial showed significant improvement in PFS with Rd vs MPT[1]
Phase III SWOG S0777 showed improvement in OS with VRd vs Rd, even in patients ≥ 65 yrs of age[2]
Daratumumab: CD38-targeted monoclonal antibody approved as single agent and in combination with standard regimens in heavily pretreated MM as well as in combination with VMP in ASCT-ineligible newly diagnosed MM
In POLLUX trial, addition of daratumumab to Rd in relapsed/refractory MM reduced risk of progression or death by 63%[3]
Current analysis: interim results from phase III trial of addition of daratumumab to Rd in transplantation-ineligible patients with newly diagnosed MM[4]
ASCT, autologous stem cell transplantation; MM, multiple myeloma; MPT, melphalan/prednisolone/thalidomide; Rd, lenalidomide/dexamethasone; VMP, bortezomib/melphalan/prednisone; VRd, bortezomib/lenalidomide/dexamethasone.
Slide credit: clinicaloptions.com
1. Benboubker. NEJM. 2014;371: Durie. ASH Abstr Dimopoulos. NEJM. 2016;375: Facon. ASH Abstr LBA-2.

4. 28-day cycles until progression
MAIA: Study Design
Randomized phase III trial
Stratified by ISS (I vs II vs III), region (N America vs other), age (< 75 vs ≥ 75 yrs)
Daratumumab 16 mg/kg IV
(QW cycles 1-2, Q2W cycles 3-6, Q4W cycle 7+) +
Lenalidomide 25 mg/day PO on Days
Dexamethasone 40 mg/wk* PO or IV
(n = 368)
Patients with ASCT-ineligible NDMM, ECOG PS 0-2,
CrCl ≥ 30 mL/min
(N = 737)
28-day cycles until progression
Lenalidomide 25 mg/day PO on Days
Dexamethasone 40 mg/wk* PO or IV
(n = 369)
ASCT, autologous stem cell transplantation; BMI, body mass index; CrCl, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; MRD, measurable residual disease; NDMM, newly diagnosed multiple myeloma; PS, performance status.
*Reduced to 20 mg/wk if > 75 yrs of age or BMI < 18.5.
Primary endpoint: PFS
Secondary endpoints : ≥ CR rate, ≥ VGPR rate, MRD negativity, ORR, OS, safety
Slide credit: clinicaloptions.com
Facon. ASH Abstr LBA-2.

5. MAIA: Patient Characteristics
Baseline characteristics well balanced between treatment arms
Characteristic
All Patients (N = 737)
Median age, yrs (range)
73 (45-90)
Male, % 52
White, % 92
ECOG PS 0/1/≥ 2, %
34/50/17
ISS stage, % I II
III 27 43 29
Disease type, %
IgG
IgA 62 18
High-risk cytogenetic profile,* n/N (%)
92/642 (14)
ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; PS, performance status.
*Defined as t(4;14), t(14;16), or del(17p).
Slide credit: clinicaloptions.com
Facon. ASH Abstr LBA-2.

6. MAIA: Patient Disposition
Outcome
Daratumumab + Rd (N = 368)
Rd (n = 369)
Patients who discontinued treatment, n (%)
118 (32)
207 (57)
Reason for discontinuation, n (%) PD AE
Death
Patient decision
Clinician decision
Other
Lost to follow-up
53 (15)
27 (7)
21 (6)
13 (4)
2 (< 1)
87 (24)
59 (16)
16 (4)
17 (5)
1 (< 1)
Median duration of treatment, mos (range)
25.3 ( )
21.30 ( )
Median cycles of therapy, n, (range)
27 (1-44)
22 (1-43)
Median relative dose intensity, % (range)
Daratumumab
Lenalidomide
Dexamethasone
98.4 ( )
76.2 ( )
84.2 ( ) --
91.4 ( )
90.7 ( )
AE, adverse event; PD, progressive disease; Rd, lenalidomide/dexamethasone.
Slide credit: clinicaloptions.com
Facon. ASH Abstr LBA-2.

7. MAIA: Efficacy Median follow-up for PFS and OS: 28 mos
Outcome
Daratumumab + Rd (n = 368)
Rd (n = 369)
HR (95% CI)
P Value
PFS
Median, mos
30 mos, % NR 71
31.9 56
0.56 ( )
< .0001 OS
Events, n (%)
62 (17)
76 (21)
0.78 ( )
ORR, %
Stringent CR CR
VGPR PR 93 30 17 32 14 81 12 28
MRD negativity, % 24 7
ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; MRD, measurable residual disease; NR, not reached; PS, performance status; Rd, lenalidomide/dexamethasone.
Median follow-up for PFS and OS: 28 mos
Daratumumab treatment favored in most subgroups analyzed, including age, race, ISS stages, ECOG PS scores
Reduced risk of progression or death with MRD negativity in both study arms
Slide credit: clinicaloptions.com
Facon. ASH Abstr LBA-2.

8. MAIA: Safety Hematologic Nonhematologic TEAE, %
Daratumumab + Rd (n = 364)
Rd (n = 365)
Any Grade
Grade 3/4
Neutropenia
Anemia
Thrombocytopenia
Lymphopenia 50 12 7 15 35 20 9 11
Diarrhea
Constipation
Fatigue
Peripheral edema
Back pain
Asthenia
Nausea
Pneumonia
DVT and/or pulmonary embolism 57 41 40 38 34 32 23 2 8 3 4 1 14 6 46 36 28 29 26 25 13
< 1
<1
Infusion-related reaction --
Invasive SPM
TEAE resulting in death
Hematologic
Nonhematologic
DVT, deep vein thrombosis; Rd, lenalidomide/dexamethasone; SPM, second primary malignancy; TEAE, treatment-emergent adverse event.
Slide credit: clinicaloptions.com
Facon. ASH Abstr LBA-2.

9. MAIA: Conclusions
Addition of daratumumab to Rd reduced risk of progression or death by 44% in patients with ASCT-ineligible newly diagnosed MM
Improved depth of response with daratumumab, including 2-fold higher stringent CR/CR rate and 3-fold improvement in MRD negativity
Safety profile of daratumumab/lenalidomide/dexamethasone in newly diagnosed MM similar to previously reported in R/R MM
Investigators suggest that these results support use of daratumumab/ lenalidomide/dexamethasone as a new standard of care in patients with newly diagnosed MM who are not eligible for ASCT
ASCT, autologous stem cell transplantation; MM, multiple myeloma; MRD, measurable residual disease; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Facon. ASH Abstr LBA-2.

10. Go Online for More CCO Coverage of ASH 2018!
Short slideset summaries and additional CME-certified analyses with expert faculty commentary on key studies in:
Leukemias
Lymphomas/CLL
Multiple Myeloma
Other Hematologic Diseases
clinicaloptions.com/oncology