Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study

Figures & data

Table 1. Demographic and baseline characteristics.

Characteristic	NDMM
	All (n = 87)	Transplant (n = 39)	Non-transplant (n = 48)
Age, years
Median (range)	63.0 (41–82)	60.0 (41–74)	66.5 (41–82)
Category, n (%)
<65	46 (52.9)	29 (74.4)	17 (35.4)
65–74	31 (35.6)	10 (25.6)	21 (43.8)
≥75	10 (11.5)	0	10 (20.8)
Male, n (%)	55 (63.2)	22 (56.4)	33 (68.8)
ECOG performance status score, n (%)
0	40 (46.0)	18 (46.2)	22 (45.8)
1	42 (48.3)	20 (51.3)	22 (45.8)
2	5 (5.7)	1 (2.6)	4 (8.3)
ISS disease stage, n (%)^a
I	30 (34.5)	14 (35.9)	16 (33.3)
II	31 (35.6)	15 (38.5)	16 (33.3)
III	26 (29.9)	10 (25.6)	16 (33.3)
Type of measurable disease, n (%)^b
IgG	47 (54.0)	22 (56.4)	25 (52.1)
IgA	14 (16.1)	5 (12.8)	9 (18.8)
Other^c	0	0	0
Urine only	17 (19.5)	8 (20.5)	9 (18.8)
Serum free light-chain	9 (10.3)	4 (10.3)	5 (10.4)
Median time from MM diagnosis to enrollment (range), months	0.08 (0.0–3.1)	0.08 (0.0–0.3)	0.08 (0.0–3.1)
Cytogenetic profile^d
N	84	37	47
Standard risk, n (%)	53 (63.1)	26 (70.3)	27 (57.4)
High risk, n (%)	31 (36.9)	11 (29.7)	20 (42.6)
del17p	7 (8.3)	3 (8.1)	4 (8.5)
t(4;14)	20 (23.8)	8 (21.6)	12 (25.5)
t(14;16)	27 (32.1)	10 (27.0)	17 (36.2)

ECOG: Eastern Cooperative Oncology Group; ISS: International Staging System; MM: multiple myeloma; NDMM: newly diagnosed multiple myeloma.

^aBased on the combination of serum β2-microglobulin and albumin.

^bIncludes patients without measurable disease in serum and urine.

^cIncludes IgD, IgM, IgE, and biclonal.

^dCytogenetic risk was based on local fluorescence in situ hybridization or karyotype analysis. Patients with high-risk cytogenetics had a del17p, t(4;14), or t(14;16) abnormality. Patients with standard-risk cytogenetic abnormalities had an absence of high-risk cytogenetic abnormalities. Analyses were per local standards in each community-based center; patients with high-risk cytogenetic abnormalities were identified if their measurement result was deemed to be above background, which has subsequently been suggested to overestimate incidence as technical thresholds have since been described at as ranging from 10% to 50% [36–38].

Figure 1. Summary of response rates over time. Data for induction cycles 1–4 are from the primary endpoint analysis [12,39]. Response data are also shown for the end of induction and end of study, occurring after all patients completed 1 year of maintenance therapy and were followed for 36 months after the start of induction therapy, died, or withdrew from the study (median follow-up at end of study: NDMM, 35.7 months). Percentages may not add to 100% due to rounding. NDMM: newly diagnosed multiple myeloma; ORR: overall response rate; VGPR: very good partial response; CR: complete response; PR: partial response; sCR: stringent complete response.

Figure 2. PFS in NDMM patients by (A) transplant status and (B) by transplant status and response. Results of the Kaplan–Meier estimates of PFS at end of study are shown by (A) transplant status among patients who received ≥1 dose of study treatment, and by (B) transplant status and response among the response evaluable population. Median PFS was not reached for any group, and estimated 24- and 36-month PFS rates are provided in the figures. The symbols for panel A are as follows: empty squares, NDMM transplant group; empty triangles, NDMM non-transplant group. For Panel B, the symbols are: empty squares, NDMM transplant with ≥CR group; filled squares, NDMM transplant with ≤VGPR group; empty triangles, NDMM non-transplant with ≥CR group; filled triangles, NDMM non-transplant with ≤VGPR group.

Table 2. Most common TEAEs of any grade (≥25%) and grade 3/4 (≥10%) in the safety analysis set.^a

Patients with ≥1 TEAE, n (%)	NDMM (n = 86)
	Any grade	Grade 3/4
Hematologic
Neutropenia	12 (14.0)	11 (12.8)
Leukopenia	8 (9.3)	5 (5.8)
Nonhematologic
Fatigue	59 (68.6)	6 (7.0)
Nausea	43 (50.0)	1 (1.2)
Cough	42 (48.8)	0
Diarrhea	38 (44.2)	4 (4.7)
Upper respiratory tract infection	30 (34.9)	0
Insomnia	28 (32.6)	0
Back pain	27 (31.4)	1 (1.2)
Dyspnea	27 (31.4)	1 (1.2)
Constipation	27 (31.4)	0
Vomiting	26 (30.2)	3 (3.5)
Headache	24 (27.9)	0
Pain in extremity	15 (17.4)	1 (1.2)
Oropharyngeal pain	12 (14.0)	0
Nasopharyngitis	11 (12.8)	0
Productive cough	8 (9.3)	0
Pneumonia	8 (9.3)	3 (3.5)
Abdominal pain	8 (9.3)	0
Myalgia	8 (9.3)	0
Sinusitis	7 (8.1)	1 (1.2)
IRRs	48 (55.8)	4 (4.7)

NDMM: newly diagnosed multiple myeloma; TEAE: treatment-emergent adverse event; IRR: infusion-related reaction.

^aThe safety analysis set includes all patients who received ≥1 dose of study treatment.

Table 3. Most common TEAEs of any grade (≥20%) and grade 3/4 (≥5%) occurring during the maintenance phase of study therapy in the safety analysis set.^a,b

	NDMM
	Transplant (n = 36)		Non-transplant (n = 39)
Patients with  ≥ 1 TEAE, n (%)	Any grade	Grade 3/4	Any grade	Grade 3/4
TEAEs occurring during maintenance therapy	36 (100.0)	13 (36.1)	34 (87.2)	10 (25.6)
Cough	16 (44.4)	0	10 (25.6)	0
Upper respiratory tract infection	11 (30.6)	0	8 (20.5)	0
Fatigue	9 (25.0)	0	7 (17.9)	1 (2.6)
Dyspnea	9 (25.0)	1 (2.8)	1 (2.6)	0
Nausea	8 (22.2)	0	4 (10.3)	0
Diarrhea	8 (22.2)	1 (2.8)	3 (7.7)	0
Pruritus	8 (22.2)	0	1 (2.6)	0
Cataract	0	0	4 (10.3)	2 (5.1)
Atrial fibrillation	0	0	2 (5.1)	2 (5.1)

NDMM: newly diagnosed multiple myeloma; TEAE: treatment-emergent adverse event.

^aThe safety analysis set includes all patients who received ≥1 dose of study treatment.

^bNo patient died due to a TEAE during maintenance phase.

Yimer H, Melear J, Faber E, et al. Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study. Br J Haematol. 2019;185(3):492–502.

 PubMed Web of Science ®Google Scholar

Rifkin RM, Melear J, Faber E, et al. Daratumumab (DARA) maintenance therapy improves depth of response and results in durable progression-free survival (PFS) following DARA plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) induction therapy in multiple myeloma (MM): update of the LYRA study. Presented at: The American Society of Hematology Annual Meeting and Exposition; 2019 December 6–10.

 Google Scholar

Data sharing statement

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.