Constantine S. Tam, MD, associate professor, Peter MacCallum Cancer Centre, discusses the side effect profile of duvelisib in patients with chronic lymphocytic leukemia (CLL).

The PI3-kinase inhibitor duvelisib is very similar to idelalisib (Zydelig) in regard to the safety profile, says Tam. Common class effects are rash, hepatitis, and the potential for pneumonitis and colitis.

In the phase III DUO trial, duvelisib was compared to ofatumumab (Arzerra) in patients with relapsed/refractory CLL or small lymphocytic lymphoma. Tam said that in this study, there were not many infections, which he attributes to the strict prophylactic measures. All patients were required to take pneumocystis pneumonia prophylaxis and were recommended to have cytomegalovirus (CMV) surveillance and prophylaxis. The patients who did develop an infection were the ones who did not adhere to the prophylaxis regimen, Tam says.

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Constantine S. Tam, MD, associate professor, Peter MacCallum Cancer Centre, discusses the side effect profile of duvelisib in patients with chronic lymphocytic leukemia (CLL).
 

Dr. Tam Discusses the Side Effect Profile of Duvelisib in CLL

Constantine S. Tam, MD, associate professor, Peter MacCallum Cancer Centre, discusses the randomized phase III DUO trial of duvelisib versus ofatumumab (Arzerra) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The phase III DUO trial investigated duvelisib, a PI3-kinase inhibitor, with the standard ofatumumab. Results showed that duvelisib was superior to ofatumumab in terms of progression-free survival (PFS). Median PFS was 13.3 months for duvelisib compared with 9.9 months in the ofatumumab arm. The drug is likely headed for an application for registration, says Tam.

This study randomized 319 patients with CLL/SLL in a 1:1 ratio to duvelisib at 25 mg twice daily until disease progression or unacceptable toxicity, or ofatumumab at 300 mg on day 1, followed by 7 weekly infusions and 4 monthly infusions of 200 mg. Duvelisib reduced the risk of death by 46%.

Constantine S. Tam, MD, associate professor, Peter MacCallum Cancer Centre, discusses, the randomized phase III DUO trial of duvelisib versus ofatumumab (Arzerra) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Dr. Tam Discusses the DUO Trial for CLL

Constantine S. Tam, MD, associate professor, Peter MacCullum Cancer Centre, discusses the toxicities associated with the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) for patients with mantle cell lymphoma (MCL).

Toxicities that were seen with the combination were what was expected from the 2 drugs individually, states Tam. Ibrutinib had side effects in terms of bruising and bleeding. Venetoclax had reflux symptoms and neutropenia, which are both expected, explains Tam. Importantly, neither one of these toxicities was higher when the drugs were given in combination compared with monotherapy.

This treatment requires 8 tablets a day, and none of the patients had to stop their treatment because of toxicities.

Dr. Tam on the Toxicity of Ibrutinib Plus Venetoclax in MCL

Constantine S. Tam, MD, associate professor, Peter MacCullum Cancer Centre, discusses the toxicities of the phase II and phase III studies investigating the combination of ibrutinib (Imbruvica) plus venetoclax (Venclexta) for patients with mantle cell lymphoma (MCL).

The toxicities were similar to what would be seen with the drugs individually. Ibrutinib had side effects in terms of bruising and bleeding. Venetoclax was associated with reflux symptoms and neutropenia. Importantly, neither of these toxicities were higher when the drugs were given in combination, explains Tam.

There were a number of patients who experienced diarrhea, which could be because this treatment requires 8 tablets a day. However, none of the patients had to stop their treatment due to adverse events, states Tam.

Dr. Tam on the Toxicities of Ibrutinib Plus Venetoclax in MCL

Constantine S. Tam, MD, associate professor, Peter MacCullum Cancer Centre, discusses the phase II and phase III studies investigating the combination of ibrutinib (Imbruvica) plus venetoclax (Venclexta) for patients with mantle cell lymphoma (MCL).

The results from the phase II study demonstrate the combination is tolerable and there were no unexpected toxicities, explains Tam. The complete remission rate was 63% and 75% of patients were minimal residual disease-negative.

The phase III study is ongoing, continuing to investigate the combination compared with ibrutinib alone, states Tam.

Dr. Tam on the Combination of Ibrutinib Plus Venetoclax in Mantle Cell Lymphoma

Constantine S. Tam, MD, associate professor, Peter MacCullum Cancer Centre, discusses BTK inhibition in chronic lymphocytic leukemia (CLL).

In a dose-escalation study, the BTK inhibitor ibrutinib (Imbruvica) was explored in patients with CLL. Most of the current available agents aren’t selective enough and have not exploited the full potential of BTK inhibition in CLL, says Tam.

Remission rates has been observed at 34% in patients with Waldenström's macroglobulinemia when BTK inhibition has been pushed with higher rates of ibrutinib. By increasing the level of BTK inhibition, remission rates have more than doubled in patients.

Dr. Tam Discusses BTK Inhibition in CLL

Constantine S. Tam, MD, associate professor, Peter MacCullum Cancer Centre, discusses BGB-3111, a new BTK inhibitor being used in the treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

In this phase I dose-escalation study, 66 patients with CLL/SLL were given BGB-3111 at escalating doses starting at 40 mg per day to 160 mg twice a day. Both previously treated and frontline patients were included in the study, which reported a response rate of 96% in early follow-up data.

Although no complete remissions have been seen yet, both relapse with mutations and Richter’s transformation have not been reported.

Currently, BGB-3111 is being used as both a single agent and in combinations in 3 phase I clinical trials focused on establishing safety and efficacy for patients with B-cell lymphoid malignancies.

Constantine S. Tam, MD, associate professor, Peter MacCullum Cancer Centre, discusses BGB-3111, a new BTK inhibitor being used in the treatment of patients with chronic lymphocytic leukemia and small lymphocytic lymphoma.

Dr. Tam on BTK Inhibitor BGB-3111 in CLL

Constantine S. Tam, MD, Consultant Hematologist, Division of Hematology and Oncology, Peter MacCallum Cancer Center, Melbourne, Australia discusses BCL2 inhibitors in chronic lymphocytic leukemia (CLL).

BCL2 inhibitors are very active in CLL. One challenge is selecting between BCL2 inhibitors and agents like Ibrutinib and idelalisib, said Tam.

Ibrutinib and idelalisib are very effective in most patients, but rarely achieve complete remission. The BCL2 inhibitor venetoclax, especially in combination with rituximab, regularly allow patients to achieve complete remission and minimal residual disease, said Tam.

A major factor in choosing one class over the over is the intention for treatment. If an oncologist wants a low-side effect therapy that will be given over a long period of time, ibrutinib and idelalisib are the ideal. If they are looking to eventually stop therapy all together a BCL2 inhibitors is the best option.

There are also combination studies combining ibrutinib with venetoclax, which may have potential.

Constantine S. Tam, MD

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