Characterization of low-grade arthralgia, myalgia, and musculoskeletal pain with ibrutinib therapy: pooled analysis of clinical trials in patients with chronic lymphocytic leukemia and mantle cell lymphoma

Figures & data

Table 1. Baseline characteristics and demographics of patients treated with ibrutinib in clinical trials.

	Total patients N = 1178
Median age, years (range)	67 (30–89)
≥65, n (%)	724 (61.5)
≥75, n (%)	235 (19.9)
Male, n (%)	834 (70.8)
Race, n (%)
White	1063 (90.2)
Black	37 (3.1)
Asian	31 (2.6)
Other/Unknown	47 (4.0)
Region, n (%)
United States	517 (43.9)
Europe	517 (43.9)
Other	144 (12.2)
Prior therapy, median (range)	2 (0–13)
3 prior therapies, n (%)	178 (15.1)
≥4 prior therapies, n (%)	264 (22.4)
CrCl^a <60 mL/min, n (%)	295 (25.0)
Hepatic impairment,^b n (%)
Not impaired	985 (83.6)
Mild impairment	166 (14.1)
Moderate impairment	15 (1.3)
Severe impairment	1 (0.1)
Missing	11 (0.9)

^aCrCl was calculated using Cockcroft-Gault formula based on creatinine values from central lab data.

^bNot impaired: TB and AST ≤ ULN; mild: ULN ≤ TB ≤ 1.5*ULN or TB ≤ ULN and AST > ULN; moderate: 1.5*ULN ≤ TB ≤ 3*ULN; severe: TB > 3*ULN.

AST: aspartate aminotransferase; CLL: chronic lymphocytic leukemia; CrCl: creatinine clearance; MCL: mantle cell lymphoma; SLL: small lymphocytic lymphoma; TB: total bilirubin; ULN: upper limit of normal.

Figure 1. Percentage of patients with the first onset of low-grade (grade 1/2) arthralgia, myalgia, and musculoskeletal pain over time (N = 1178).

Table 2. Summary of arthralgia, myalgia, and musculoskeletal pain and concomitant medication use for patients treated with ibrutinib (RESONATE-2/iLLUMINATE dataset).

	Total patients N = 248
Patients reporting any arthralgia event, n (%)	48 (19)
Patients reporting ≥ 1 low-grade arthralgia event, n (%)	46 (19)
With prior concomitant medications, n (%)	5 (2)
Given concomitant medications following:
First reported event, n (%)	9 (4)
First event symptoms resolved, n (%)	9 (4)
Received steroids, n (%)	2 (1)
Received NSAIDs, n (%)	6 (2)
Received opioids/phenylpiperidine derivatives, n (%)	2 (1)
Second reported event, n (%)	3 (1)
Second event symptoms resolved, n (%)	3 (1)
Received steroids, n (%)	1 (0.4)
Received NSAIDs, n (%)	3 (1)
Received opioids/phenylpiperidine derivatives, n (%)	1 (0.4)
Received other analgesics, n (%)	1 (0.4)
Patients reporting any myalgia event, n (%)	15 (6)
Patients reporting ≥ 1 low-grade myalgia event, n (%)	14 (6)
With prior concomitant medications, n (%)	1 (0.4)
With concomitant medications following:
First reported event, n (%)	0
Patients reporting any musculoskeletal pain event, n (%)	17 (7)
Patients reporting low-grade musculoskeletal pain, n (%)	16 (6)
With prior concomitant medications, n (%)	0
Given concomitant medications following:
First reported event, n (%)	5 (2)
First event symptoms resolved, n (%)	5 (2)
Received NSAIDs, n (%)	3 (1)
Received opioids/phenylpiperidine derivatives, n (%)	2 (1)
Received steroids, n (%)	1 (0.4)
Received other analgesics, n (%)	2 (1)
Received other, n (%)	1 (0.4)

NSAIDs: nonsteroidal anti-inflammatory drugs.

Figure 2. The proportion of patients with one, two, or three events of low-grade (grade 1/2) arthralgia, myalgia, and musculoskeletal pain in those treated with ibrutinib in clinical trials (N = 1178) AE: adverse event.

Figure 3. The proportion of patients (RESONATE-2/iLLUMINATE dataset) with low-grade (grade 1/2) arthralgia, myalgia, and musculoskeletal pain given concomitant medications to manage these AEs. AE: adverse event.

Data availability statement

Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu