Michael Wang, MD, discusses the impact of acalabrutinib in patients with mantle cell lymphoma, the implications of the phase 2 ACE-LY-004 trial, and the challenges faced with treating those who harbor TP53 mutations.
Acalabrutinib (Calquence) continued to showcase robust activity and durable responses in patients with relapsed/refractory mantle cell lymphoma (MCL) at 38.1 months of follow-up, which confirms that the agent is highly active in this population, according to Michael Wang, MD.
Updated results from the phase 2 ACE-LY-004 trial (NCT02213926) showed that the agent elicited an overall response rate (ORR), with a complete response rate of 48%.1 Notably, the ORR was not found to be significantly different for patients who received 1, 2, or 3 or more prior lines of therapy, at 83.1%, 86.5%, and 71.4%, respectively.
The median overall survival achieved with acalabrutinib was 59.2 months (95% CI, 36.5–not evaluable), and was consistent across subgroups. Moreover, the median duration of response (DOR) and the median progression-free survival (PFS) were 29 months and 22 months, respectively. The median overall survival was 59.2 months overall. In those who received 2 or more prior therapies, the median OS was 55.9 months; it had not yet been reached in those who received 1 prior therapy.
“For a single agent, after 2 prior lines of therapy, these are remarkable data,” Wang said.
In an interview with OncLive® during the 2021 Pan Pacific Lymphoma Conference, Wang, a professor of lymphoma and melanoma at The University of Texas MD Anderson Cancer Center, discussed the impact of acalabrutinib in patients with MCL, the implications of the phase 2 ACE-LY-004 trial, and the challenges faced with treating those who harbor TP53 mutations.
Wang: I had the privilege to present the long-term [data] on single-agent acalabrutinib in [patients with] relapsed MCL. The original study was published in Lancet Oncology in 2017. This clinical trial with single-agent acalabrutinib in patients with relapsed MCL after 2 prior lines of therapy was paved the way to the FDA approval of the drug in 2017.
The 38-month follow-up on this clinical trial showed that the response rates are still very high, at 81%. The CR rate is much higher than before, at 48%. Most importantly, the DOR was [approximately] 29 months, and [the median] PFS was 22.0 months. Remarkably, these patients have survived [a median of about] 59 months. These data indicated that acalabrutinib is a good therapy [for use] as a monotherapy in relapsed MCL.
It is important to clarify that although data [in chronic lymphocytic leukemia show that 17p deletion (del[17p])] is a very negative prognostic factor, in MCL, there is [debate] about this. Del(17p) has not been uniformly reported to be associated with negative prognoses in MCL, and therefore, it is not [thought to be] as important as [it is] in CLL.
TP53 needs to form a tetramer to be functional. If even 1 of the monomers in the tetramer contains a mutation, it will render the monomer nonfunctional. Therefore, the whole tetramer will not be functional. If the TP53 is not functioning, [it will result in] resistant and aggressive MCL. [The data show that patients with] TP53 mutations are prognostically [worse] than those with del(17p). This is the other issue that we hope to overcome.
CAR T-cell therapies and multiple combination therapies of about 3 agents [are under examination]. Thus far, single agents and doublet [approaches], have not been reported to overcome TP53 mutations in MCL.