Phase II Study of Single-Agent and Combination Everolimus and Panobinostat in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Figures & data

Figure 1. Planned accrual design. (a) Schema for sequential single-agent lead-in to doublet therapy. (b) Following a protocol amendment, sequential lead-in was eliminated and all patients were enrolled to doublet therapy upfront.

Figure 2. Enrollment. IF: informed consent; PI: principal investigator.

Table 1. Baseline patient characteristics.

	Part 1, Arm A Everolimus first N = 9	Part 1, Arm B Panobinostat first N = 6	Part 2 Doublet N = 18
Age, in years	64 (47–77)	67 (51–83)	65 (26–77)
Gender
M/F^d	3 (33.3)/6 (66.6)	5 (83.3)/1 (16.7)	15 (83.3)/3 (16.7)
Race
White	8 (88.9)	6 (100)	17 (94.4)
Black	1 (11.1)	0 (0.00)	1 (5.56)
Hispanic	0 (0.00)	0 (0.00)	0 (0.00)
Median # Prior therapies	2 (2–6)	3 (1–5)	4 (1–7)
History of HSCT^a	2 (22.2)	0 (0.00)	10 (55.6)
Refractory^b	7 (77.8)	4 (66.7)	11 (61.1)
History of XRT^c	4 (44.4)	1 (16.7)	8 (44.4)

Continues variables reported as median, (range). Discrete variables are reported as n (%).

^aHSCT: hematopoietic stem cell transplant. ^bRefractory to most recent therapy. ^cXRT: radiation therapy. ^dMale/Female.

Table 2. Best response by treatment arm and drug.

Best response	Part 1, Arm A Everolimus first N = 9		Part 1, Arm B Panobinostat first N = 6		Part 2 Doublet N = 18	p-Value^d
	Everolimus n = 9/9	Panobinostat n = 6/9	Panobinostat n = 6/6	Everolimus n = 2/6		0.665
CR/PR^a	1 (11.1)	0 (0.0)	0 (0.0)	0 (0.0)	4 (25.0)
SD/PD^b	8 (88.9)	4 (100.0)	5 (100.0)	2 (100.0)	12 (75.0)
Non-evaluable^c	0	2	1	0	2

Discrete variables are reported as n (%).

^aCR: complete response; PR: partial response. ^bSD: stable disease; PD: progressive disease. ^cNon-evaluable patients were not included in response analysis calculation. ^dFischer’s exact test p-value.

Table 3. Adverse events.

		Part 1, Arm A Everolimus first N = 9	Part 1, Arm B Panobinostat first N = 6	Part 2 Doublet N = 18
Patients with any AE^a		9 (100)	6 (100)	18 (100)
Patients with any Grade 3/4 AE		7 (77.8)	5 (83.3)	18 (100)
Patients with any SAE^b		2 (22.2)	1 (16.7)	9 (50.0)
Grade 3/4 AE
Everolimus single agent
Anemia		1 (11.1)	0 (0.00)	–
Thrombocytopenia		0 (0.00)	2 (33.3)	–
Abdominal distension		1 (11.1)	0 (0.00)	–
Hypertension		1 (11.1)	0 (0.00)	–
Hypertriglyceridemia		1 (11.1)	0 (0.00)	–
Headache		1 (11.1)	0 (0.00)	–
Panobinostat single agent
Anemia		1 (11.1)	0 (0.00)	–
Thrombocytopenia		2 (22.2)	5 (83.3)	–
Neutropenia		0 (0.00)	1 (16.7)	–
Diarrhea		1 (11.1)	0 (0.00)	–
Nausea		1 (11.1)	0 (0.00)	–
Encephalopathy		1 (11.1)	0 (0.00)	–
Musculoskeletal pain		1 (11.1)	1 (16.7)	–
Doublet
Anemia		–	–	3 (16.7)
Thrombocytopenia		–	–	15 (83.3)
Neutropenia		–	–	6 (33.3)
Atrial flutter		–	–	1 (5.56)
Pericardial effusion		–	–	1 (5.56)
Edema		–	–	1 (5.56)
Pulmonary embolism		–	–	1 (5.56)
Hypoxia, pneumonitis		–	–	2 (11.1)
Abdominal pain		–	–	1 (5.56)
Vomiting		–	–	1 (5.56)
Diarrhea		–	–	1 (5.56)
Colitis		–	–	1 (5.56)
Anorexia		–	–	1 (5.56)
Hypovolemia		–	–	1 (5.56)
Septic shock		–	–	1 (5.56)
Fatigue		–	–	10 (55.6)
Hyponatremia		–	–	2 (11.1)
Hyperglycemia		–	–	2 (11.1)
SAE
Everolimus single agent
Abdominal distension		1 (11.1)	0 (0.00)	–
Panobinostat single agent
Musculoskeletal pain		0 (0.00)	1 (16.7)	–
Encephalopathy		1 (11.1)	0 (0.00)	–
Doublet
Atrial flutter		–	–	1 (5.56)
Pericardial effusion		–	–	1 (5.56)
Hypoxia, pneumonitis		–	–	1 (5.56)
Colitis		–	–	1 (5.56)
Hypovolemia		–	–	1 (5.56)
Vomiting		–	–	1 (5.56)
Fatigue		–	–	2 (11.1)
Septic shock		–	–	1 (5.56)
Cellulitis		–	–	1 (5.56)

Discrete variables are reported as n (%). Toxicity was graded using the CTCAE version 4.0 (http://ctep.info.nih.gov). Any patient who received a dose of study drug was included for toxicity evaluation.

^aAE: adverse event. ^bSAE: serious adverse event.