Paolo Ghia, MD, PhD is a Full Professor in Medical Oncology at the Università Vita-Salute San Raffaele and Head of the Laboratory of B-Cell Neoplasia at the affiliated IRCCS Ospedale San Raffaele. He is Director of the Strategic Research Program on CLL, a clinical Unit at the hospital, where he acts as National Coordinator or Principal Investigator in Phase 1-3 clinical trials in CLL.

Paolo Ghia, MD, PhD, full professor, Medical Oncology, head, Strategic research program on CLL Università Vita Salute San Raffaele, deputy director, Division of Experimental Oncology, San Raffaele Scientific Institute, discusses the rationale for the phase 2 CAPTIVATE trial (NCT02910583) in chronic lymphocytic leukemia (CLL).

The CAPTIVATE trial evaluated the fixed-duration combination ibrutinib (Imbruvica) plus venetoclax (Venclexta) as first-line treatment for patients with CLL or small lymphocytic lymphoma. 

The rationale for the study was based on the synergistic effects demonstrated by combining ibrutinib and venetoclax, says Ghia. Single-agent ibrutinib can relieve cancer cells from the lymphoid tissue microenvironment into circulation where they are prone to undergo apoptosis, Ghia explains.

The addition of venetoclax will exacerbate that effect and lead to more effective apoptosis, Ghia says. In turn, resting and dividing leukemic cells can be eliminated, Ghia adds. Additionally, proliferative CLL cells can be mobilized out of lymph nodes and other protective lymphoid niche areas, which prevents further disease from developing, concludes Ghia.

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Paolo Ghia, MD, PhD, discusses the rationale for the phase 2 CAPTIVATE trial in chronic lymphocytic leukemia.



Dr. Ghia on the Rationale for the CAPTIVATE Trial in CLL 

Paolo Ghia, MD, PhD, a professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Università Vita-Salute San Raffaele University, discusses results seen with the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).

Results from the phase 3 GLOW trial (NCT03462719) showed that the combination of ibrutinib and venetoclax was very effective among elderly patients with CLL, according to Ghia. Many were able to achieve undetectable minimal residual disease (MRD), yielding deep responses in the peripheral blood were reported in approximately 80% of patients at any time during treatment, with similar results seen in the bone marrow, Ghia says.

Interestingly, the durability of response may possibly be more important than the depth of response, Ghia notes. Of the patients who achieved undetectable MRD, 80% were still MRD-negative after 12 months of follow up, Ghia concludes.

Paolo Ghia, MD, PhD, discusses results seen with the combination of ibrutinib and venetoclax as a first-line treatment for patients with chronic lymphocytic leukemia.


Dr. Ghia on the Efficacy of Ibrutinib/Venetoclax in CLL

Paolo Ghia, MD, PhD, a professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Università Vita-Salute San Raffaele University, discusses overall survival (OS) data with acalabrutinib (Calquence) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 ASCEND trial.

At the moment, an OS advantage was no observed with acalabrutinib compared with idelalisib (Zydelig) plus rituximab (Rituxan) or bendamustine plus rituximab, says Ghia. Nowadays, this is typical in the new trials because patients on the control arm, upon disease progression, had the opportunity to switch over to acalabrutinib, explains Ghia. This crossover affected the OS and showed the relevance of the treatment that is provided to these patients, concludes Ghia.

Paolo Ghia, MD, PhD, discusses overall survival data with acalabrutinib in patients with relapsed/refractory chronic lymphocytic leukemia in the phase 3 ASCEND trial.

Dr. Ghia on Lack of OS Advantage With Acalabrutinib Per ASCEND Trial in CLL

Paolo Ghia, MD, PhD, a professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Vita-Salute San Raffaele University, discusses how use the of chemotherapy is decreasing in favor of novel agents in chronic lymphocytic leukemia (CLL).

Chemotherapy regimens and chemoimmunotherapy treatment approaches are fading out of the treatment algorithm of CLL, says Ghia. This shift will be seen in the updated ASCO guidelines, where chemoimmunotherapy only remains an option for patients who do not have access to the novel therapies that are currently available in some countries and regions.

Not everyone has the same accessibility, but for the patients who do, particularly in the first-line setting, most of them experience a benefit from novel therapies. Even in the relapsed/refractory setting, the percentage of patients who benefit from chemoimmunotherapy is reducing with time, concludes Ghia.

Paolo Ghia, MD, PhD, discusses how use the of chemotherapy is decreasing in favor of novel agents in chronic lymphocytic leukemia.

Dr. Ghia on the Shift From Chemotherapy to Novel Agents in CLL


Paolo Ghia, MD, PhD, a professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Università Vita-Salute San Raffaele University, discusses the efficacy and safety of acalabrutinib (Calquence) in the phase 3 ASCEND trial in relapsed/refractory chronic lymphocytic leukemia (CLL). 

Final data from the trial were presented at the 

, and showed favorable efficacy with acalabrutinib over the physician’s choice of rituximab (Rituxan) in combination with either idelalisib (Zydelig) or bendamustine. Acalabrutinib is a second-generation BTK inhibitor, and BTK inhibition is a mainstay in the treatment of patients with CLL, says Ghia. Acalabrutinib appears to be very effective when compared with novel agent, such as idelalisib, plus rituximab, or a standard chemotherapy, such as bendamustine, plus rituximab. The data observed with acalabrutinib are comforting and prove that this agent is another tool that can be added to the treatment armamentarium, says Ghia.

Additionally, acalabrutinib showed a favorable toxicity profile and appeared to be safer than the combination of idelalisib plus rituximab, with a lower frequency of treatment discontinuation, concludes Ghia.

Paolo Ghia, MD, PhD, discusses the efficacy and safety of acalabrutinib in the phase 3 ASCEND trial in relapsed/refractory chronic lymphocytic leukemia.

Dr. Ghia on Efficacy and Safety of Acalabrutinib in Relapsed/Refractory CLL

Paolo Ghia, MD, PhD, professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Vita-Salute San Raffaele University, discusses updated results from the phase 3 ASCEND trial in relapsed/refractory chronic lymphocytic leukemia (CLL). 

, final data from the ASCEND trial continued to show favorable efficacy with acalabrutinib (Calquence) over physician’s choice of rituximab (Rituxan) in combination with either idelalisib (Zydelig) or bendamustine. 

At a median follow-up of 22 months, the median progression-free survival had not yet been reached with acalabrutinib versus 16.8 months with physician’s choice. Additionally, at 18 months of follow up, 82% of patients were alive and free from disease progression with acalabrutinib compared with 48% with the control regimen. 

Acalabrutinib demonstrated continued tolerability and no unexpected safety signals were observed, concludes Ghia.

Paolo Ghia, MD, PhD, discusses updated results from the phase 3 ASCEND trial in relapsed/refractory chronic lymphocytic leukemia. 



Dr. Ghia on Updated ASCEND Trial Results in Relapsed/Refractory CLL

Paolo Ghia, MD, assistant professor, Universitá Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, discusses the efficacy results of the ASCEND trial, which examined the use of acalabrutinib (Calquence) monotherapy in patients with previously treated chronic lymphocytic leukemia (CLL).

Results of the ASCEND trial showed that acalabrutinib is more effective than rituximab (Rituxan)/idelalisib (Zydelig) and rituximab/bendamustine in patients with previously treated CLL, Ghia explains. Acalabrutinib alone did not reach its median progression-free survival, which was around 16 months for the other 2 arms, according to Ghia.

Additionally, acalabrutinib has a better toxicity profile than rituximab/idelalisib and rituximab/bendamustine, says Ghia. For example, almost 50% of the patients treated with rituximab/idelalisib reported cases of diarrhea and colitis, whereas diarrhea was much less frequent with acalabrutinib and colitis was nonexistent. Patients who received acalabrutinib might have experienced bleeding, which is present in 25% of patients who receive BTK inhibitors, or a transient headache, which is typical. These adverse events need to be evaluated with a longer follow-up, Ghia concludes.

Paolo Ghia, MD, discusses the efficacy results of the ASCEND trial, which examined the use of acalabrutinib monotherapy in patients with previously treated chronic lymphocytic leukemia.

Paolo Ghia, MD

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