iwCLL 2017 | Venetoclax plus rituximab is highly active in patients with relapsed/refractory CLL/SLL

During iwCLL, on 15^th May 2017, the “Additional Therapies for the Relapsed/Refractory CLL Patient” session took place and was co-chaired by Michael Keating (MD Anderson Cancer Center) and Jacqueline Barrientos (The Feinstein Institute for Medical Research).

During this session, Danielle Brander, MD, from the Duke Cancer Institute, Durham, North Carolina, USA, gave a talk titled “Durability of Responses on Continuous Therapy and Following Drug Cessation in Deep Responders with Venetoclax and Rituximab.”

Adverse events were graded using the NCI CTCAE v4.0. The iwCLL 2008 criteria was used to evaluate responses including CT or MRI imaging (at end of combination therapy i.e. month 7); CT scans were undertaken every 3–6 months thereafter for all patients. The bone marrow was assessed for MRD using ≥4 color flow cytometry in local laboratories (minimum sensitivity: 0.01%).

• Best objective response:
  • ORR = 86%; CR/CRi = 51%; nPR/PR = 35%
  • SD = 8%
  • PD = 4%
  • Non-evaluable (1 patient due to fatal TLS) = 2%
• All patients experienced AEs; the most common were upper respiratory tract infection, neutropenia, and mil GI issues
• Grade 3–4 AEs occurred in 37 patients (76%); the most common were neutropenia (53%), thrombocytopenia (16%), and anemia (14%)

*TLS, n=1; worsening of peripheral neuropathy, n=1
	All Patients
Enrolled, n	49
Median (range) time on study, months	38 (<1–53)
Active patients, n	28
Median (range) time on venetoclax, months	40 (28–53)
Discontinuation due to CLL progression, n	7
Discontinuation due to Richter’s transformation, n	5
Other reasons for discontinuation, n	5
AE related to venetoclax	2*
AE considered not related to therapy	1
Withdrew consent	2
Elected to stop venetoclax after response per protocol, n	16

• Median time to CLL progression (n=7): 28 months (range, 12–50)
• Median time to Richter’s transformation (n=5): 5 months (range, 1–9)
• Time on therapy before discontinuation varied according to the protocol version active:
  • Amendment 1 (May–Sept 2012): patients discontinue treatment after achieving CR/CRi
  • Amendments 2 & 3 (Sept 2012–May 2015): patients who achieved CR/CRi and marrow MRD-negativity could discontinue therapy
  • Amendment 4 (May 2015 onward): patients who achieved marrow MRD-negativity (CR/CRi or PR) could discontinue therapy
• Re-initiation of venetoclax and followed by rituximab was permitted if patients experienced disease progression, as determined by iwCLL criteria

• Before discontinuations, median time on therapy was 16 months (range, 5–38)
• After a median of 20 months (range, 6–40), 10/12 active patients remain progression-free off therapy
• The demographics and disease characteristics of the 16 patients who chose to discontinue therapy were similar to the total study population
• 3 patients with del(17p) and 1 patient with mutant TP53 achieved MRD-negativity and were progression-free at study discontinuation or remain progression-free off venetoclax

Danielle Brander summarized her talk with a concise conclusion slide: