Jessica Skarzynski

A phase 3 study, evaluating the efficacy of Aliqopa (copanlisib) in combination with Rituxan (rituximab) in patients with indolent non-Hodgkin’s lymphoma (iNHL) who have relapsed after at least one previous line of therapy involving Rituxan, has met its primary end point of prolonged progression-free survival (PFS).

The randomized, double-blind, placebo-controlled CHRONOS-3 trial consisted mostly of patients with follicular lymphoma and marginal zone lymphoma, as well as patients with small lymphocytic lymphoma and lymphoplasmacytoid lymphoma/Waldenström’s macroglobulinemia.

“Indolent forms of non-Hodgkin’s lymphoma are a heterogenous group of malignancies characterized by a chronic pattern of remissions and recurrences. For iNHL patients with disease progression who are in need of treatment, there are few approved treatment options,” Scott Z. Fields, MD, senior vice president and head of Oncology Development at Bayer, Aliquopa’s manufacturer, said in a 

. “The positive results from CHRONOS-3 demonstrate the potential clinical benefit of copanlisib in combination with rituximab, to address the unmet medical need in these patients.”

In the trial, researchers investigated whether Aliqopa is superior to placebo in combination with Rituxan in extending PFS in patients with relapsed iNHL who have received at least one prior treatment that included Rituxan. To enroll in the trial, patients must have relapsed after their last Rituxan-containing therapy and either had a treatment-free interval of 12 months or greater after completion of the last Rituxan-containing treatment, been unwilling to receive chemotherapy or have chemotherapy be contraindicated due to age, comorbidities, and/or residual toxicity.

A total of 458 patients were enrolled, and according to the Bayer, the safety of Aliqopa has also been found to be consistent with previously published data on the individual components of the combination. No new safety signals have been identified.

In addition to discussing the data from this study with health authorities around the world, Bayer noted that results will be presented at an upcoming scientific congress.

Aliqopa was previously approved in the US under accelerated approval in 2017 for the treatment of adult patients with relapsed follicular lymphoma who have received at least two prior systemic therapies, after the open-label, single-arm, multicenter, phase 2 CHRONOS-1 clinical trial produced an overall response rate (ORR) of 59%, including a complete response rate of 14%. 

In that study, 142 patients were enrolled, including 104 patients with follicular B-cell non-Hodgkin lymphoma who had relapsed disease following at least two prior treatments. However, the release concluded continued approval for this indication will be contingent upon verification and description of clinical benefit in a confirmatory trial.

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A study evaluating the efficacy of Aliqopa (copanlisib) in combination with Rituxan (rituximab) in patients with indolent non-Hodgkin’s lymphoma who have relapsed after at least one prior line of therapy also involving Rituxan has met its primary endpoint, according to Aliqopa’s manufacturer, Bayer.  

Aliqopa in Combination with Rituxan Meets Primary End Point for Indolent Non-Hodgkin’s Lymphoma

When it comes to treating follicular lymphoma, future treatment paradigms may involve harnessing a patient’s immune system to help fight cancer, according to one expert.

’s sister publication, recently spoke with Dr. Connie L. Batlevi, a medical oncologist specializing in lymphoma at Memorial Sloan Kettering Cancer Center, about the follicular lymphoma treatment landscape and adding immunotherapy to it, which has shown encouraging data of late.

In particular, Batlevi said, using the patient’s immune system to modulate the disease is of interest to clinicians. Current studies are also looking at the efficacy of CAR-T cell therapy, antibody​-drug conjugates, and bispecific antibodies, Batlevi said. Future research should also work on identifying the right sequence of therapies is going to be key for patients, she concludes.

So, in terms of novel treatments and combinations of treatments that are coming down the pipeline, I think the things are of interest are sort of using the immune system to modulate the disease course of follicular lymphoma. We have seen promising data for chimeric antigen receptor T-cells in follicular lymphoma. CAR-T cells, we've also seen some interesting data using antibody drug conjugates. We are looking at the data for specific antibodies for follicular lymphoma.

And (while) all of those are very intriguing, how to put them in context and how to how to strategize or the sequencing of those for our patients will be important in the next several years.

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Follicular lymphoma treatment options are changing, and according to one expert, immunotherapy could become a major part of therapy sequencing. 

Follicular Lymphoma Treatment Could Rely on Immunotherapy in Therapy Sequencing

While the National Institute of Health reports that follicular lymphoma has a five-year relative survival rate of 89%, follicular lymphoma has the potential to become aggressive, making it harder to treat, says Dr. Kami J. Maddocks.

’s sister publication, Maddocks, an associate professor of clinical internal medicine in the Division of Hematology at The Ohio State University Comprehensive Cancer Center–James, examined the challenges that exist in treating patients with follicular lymphoma.

In particular, Maddocks noted, patients who relapse within 24 months of completing their first therapy tend to have a more aggressive disease, making it harder for oncologists to find treatments that will produce long-term results.

Follicular lymphoma that turns into aggressive, incurable lymphoma is another challenging issue, according to Maddocks. In these cases, allogeneic transplant is an option, but patients will need to be in treatment for the rest of their lives.

Probably our biggest challenge in patients with treating follicular lymphoma is those patients that we define as the early relapses. So those patients that progress within 24 months of completing their initial therapy, these patients have more aggressively behaved disease, and it's harder to get them long term responses and long-term remissions. This is the greatest challenge we face and there are ongoing trials right now looking at the best treatment for these patients.

When follicular (lymphoma) transforms to aggressive lymphoma, that also represents a challenge for patients. And then this is still you know, outside of an allogeneic transplant, which is rarely done not a curable disease. So, these are treatments, patients are going to deal with this disease on and off for the rest of their life. And so, finding effective, long-lasting and tolerable treatments is really a goal here.

Dr. Kami J. Maddocks discusses the importance of effective treatments for patients with aggressive follicular lymphoma and the treatment challenges they face.

Expert Discusses the Need for Safe and Effective Treatments for Aggressive Follicular Lymphoma

Neoadjuvant chemotherapy of intense dose-dense Ellence (epirubicin), Taxol (paclitaxel), and Cytoxan (cyclophosphamide) (iddEPC) offered significant disease-free survival benefits in patients with HR+/HER2- breast cancer, according to data presented at the 2020 ESMO Virtual Congress.

As well as comparing iddEPC to weekly Taxol and Doxil (liposomal doxorubicin) (PM) in patients with high-risk early breast cancer, the GeparOcto trial also examined the addition of Paraplatin (carboplatin) in patients with triple-negative breast cancer (TNBC).

In the review presented at ESMO, researchers reported on the secondary endpoint of invasive disease-free survival (iDFS), defined as the time from randomization until any invasive local regional or distant recurrence, a new contra-lateral breast cancer, a secondary malignancy or death, whichever occurred first. Overall survival (OS) was an additional secondary endpoint.

The GeparOcto trial enrolled a total of 961 patients who were first broken into three groups by breast cancer subtype:

HR+/HER2- versus HER2-/HR- versus HER2+/HR+/-

Ki67 at baseline (less than or equal to 20% versus greater than 20%), and

These patients were then split into two groups: the iddEPC arm (470 patients) received nine cycles of intensified dose-dense Ellence, Taxol, and Cytoxan, every two weeks, and the PM(Cb) arm (475 patients) received weekly Taxol plus Doxil for 18 weeks.

In both treatment arms, patients with HER2+ breast cancer additionally received Herceptin (trastuzumab) every two weeks and Perjeta (pertuzumab) every three weeks concurrently with each Taxol and Paraplatin cycle. Patients with TNBC also received weekly Paraplatin.

Between December 2014 and June 2016, a total of 945 patients started treatment. After a median follow-up of 47 months, 162 iDFS events were reported, the majority of which were distant relapses (47 in iddEPC versus 51 in PM(Cb)) and invasive locoregional relapses (18 versus 24). Additionally, 79 deaths were reported (41 in the iddEPC arm and 38 in the PM(Cb) arm).

When examining survival benefits, researchers found no significant difference in survival rates between the HER2+ or TNBC subgroups.

Additionally, investigators found no difference in iDFS or OS between both arms, with four-year iDFS at 81.9% following iddEPC versus 79.7% in PM(Cb). Overall survival after four years was 90.6% and 90.3% respectively.

However, four-year iDFS was significantly longer in the HR+/HER2- subgroup of the iddEPC arm (77.9% versus 62.5% PM), which indicated a benefit in four-year OS (80.1% versus 94.7% respectively).

In an exploratory analysis, researchers found that in patients with a higher likelihood of relapse following neoadjuvant chemotherapy based on their CPS-EG score, which calculates the risk of relapse following neoadjuvant chemotherapy, those with HR+/HER2- breast cancer were 3.5 times more likely to experience an iDFS event following weekly PM(Cb) compared to those who received iddEPC.

Despite the lack of evidence of improved survival, the iDFS benefit supports the idea that neoadjuvant chemotherapy could have an additional effect in patients with luminal-like, HER2-negative breast cancer, according to Andreas Schneeweiss, the lead author of the paper. These benefits could be possibly due to the inclusion of cytotoxic agent cyclophosphamide.

“Cyclophosphamide might play an important role in adjuvant treatment of patients with high risk, HR+/HER2- breast cancer, maybe due to an immunogenic long-term effect, not indicated by pCR and CPS-EG score,” concluded Schneeweiss.

Researchers found that neoadjuvant chemotherapy with intense dose-dense Ellence (epirubicin), Taxol (paclitaxel), and Cytoxan (cyclophosphamide) (iddEPC) demonstrated significant disease-free survival benefits in the treatment of patients with HR+/HER2- breast cancer.

Author | Jessica Skarzynski

Aliqopa in Combination with Rituxan Meets Primary End Point for Indolent Non-Hodgkin’s Lymphoma

Follicular Lymphoma Treatment Could Rely on Immunotherapy in Therapy Sequencing

Expert Discusses the Need for Safe and Effective Treatments for Aggressive Follicular Lymphoma

Dose-Dense Chemotherapy Improves Disease-Free Survival in HR+/HER2- Breast Cancer