Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma

Figures & data

Figure 1. Treatment schema. IV: intravenous; PO: orally. Ibrutinib was administered on days 1–28 of a 28-day cycle. Lenalidomide was administered on days 1–21 of a 28-day cycle. Dose-limiting toxicities were assessed during the first treatment cycle.

Table 1. Baseline characteristics.

Characteristics	Patients N = 25 n (%)
Age, median years (range)	61 (39–79)
Male	19 (76)
Prior lines of therapy, median (range)	1 (1–4)
1	14 (56)
2	7 (28)
3	3 (12)
4	1 (4)
Primary refractory	3 (12)
Refractory to last line of therapy	8 (32)
Prior treatment regimens^a
HCVAD-like^b	19 (76)
R-CHOP-like^c	1 (4)
BR	3 (12)
R-BAC	3 (12)
Other^d	6 (24)
Prior transplant	3 (12)
Autologous	2 (8)
Allogeneic	1 (4)
ECOG PS
0	12 (48)
1	13 (52)
MIPI
High (<6.2)	8 (32)
Intermediate (5.7 to ≤6.2)	11 (44)
Low (≤5.7)	6 (24)
Blastoid histology^e, n/total n (%)	6/23 (26)
Ki-67 > 30%^e, n/total n (%)	9/22 (41)
SOX11 expression^e, n/total n (%)	16/19 (84)
Overexpression of p53 positive by IHC^e, n/total n (%)	7/21 (33)

HCVAD = hyper-fractionated cyclophosphamide, vincristine, Adriamycin (doxorubicin), dexamethasone; R-CHOP = rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), prednisone; R-BAC = rituximab, bendamustine, cytarabine; ECOG PS = Eastern Cooperative Oncology Group performance status; MIPI = Mantle cell lymphoma International Prognostic Index; VR-CAP = Velcade (bortezomib), rituximab, cyclophosphamide, Adriamycin (doxorubicin), prednisone.

^a Total number of patients exceeds 25 as some patients received more than 1 prior line of therapy.

^b Defined as receipt of HCVAD, HCVAD + bortezomib, or R-DHAP alternating with HCVAD.

^c Defined as receipt of R-CHOP or VR-CAP regimens.

^d Recipient of previous clinical trial (n = 1) or unknown (n = 1).

^e Unknown or missing data: blastoid (n = 2); Ki-67 > 30% (n = 3); SOX11 expression (n = 6); overexpression of p53 positive by IHC (n = 4).

Table 2. Grade ≥3 adverse events.

Adverse events	Grade ≥3 N = 24^a n(%)
Rash	8 (33)
Neutropenic Fever	6 (25)
Infection	4 (17)
Severe Diarrhea	4 (17)
Neutropenia	2 (8)
Paroxysmal atrial fibrillation/flutter	1 (4)
Myocardial Infarction	1 (4)
Pleural Effusion	1 (4)
Hypertension	1 (4)
Syncope	1 (4)
Neurological deficit	1 (4)
Elevated liver enzymes	1 (4)

^a One patient was not evaluable for toxicity or response assessment due to early discontinuation.

Figure 2. Best response in evaluable patients. Response was evaluated after cycles 2, 4, 6 and then every 3 cycles thereafter until disease progression or discontinuation of study using Cheson criteria 2007. Best overall response was defined as the percentage of patients who achieved a CR or PR. Clinical benefit rate was defined as the percentage of patients who achieved CR, PR, or SD for at least 2 months. One patient who was not evaluable for response was excluded.

Figure 4. Duration of response. CR: complete response; PR: partial response; SD: Stable disease; PD: progressive disease. Duration of response in 24 evaluable patients. Duration of response was defined as the number of months from first documented response to the date of first event (disease progression or death) or censoring prior to the data cutoff. One patient who was not evaluable for response was excluded.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, AI. The data are not publicly available due to their containing information that could compromise the privacy of research participants. The study involves a review of the electronic medical records of mantle cell lymphoma patients who received R2I. The research data set has removed most, but not all protected health information (for example: actual dates of response assessments and treatment were included as needed for analysis but would be considered PHI). The dataset is also considered property of Hackensack Meridian Health and not owned by the investigators. Therefore, for both reasons, the dataset cannot be made openly available. However, upon request we are willing to share portions of the data for appropriate review. Requests can be made through the corresponding author or directly to representatives of Hackensack Meridian Health (Dr. Andrew Ip; Email: [email protected]).