R-CHOP Treatment for Non-Hodgkin Lymphoma

Research demonstrates that some patients with NHL can be treated with 4 instead of 6 cycles of R-CHOP.

Rituxan® (rituximab) combined with cyclophosphamide, doxorubicin, Oncovin® and prednisone (R-CHOP) is the standard of care for many patients with Non-Hodgkin’s lymphoma (NHL). Although R-CHOP is the standard researchers continue to try to improve R-CHOP treatment either by adding additional drugs to the regimen in NHL patients at high risk of recurrence or be reducing the total treatment in low risk individuals. Most recently doctors from Germany have reported that 4 cycles of R-CHOP treatment is just is good as 6 cycles in certain low risk individuals. (1) All NHL patients should understand the role of R-CHOP and the research being conducted to improve its effectiveness.

Frequently Asked Questions About R-CHOP

What is R-CHOP Chemotherapy?

CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is a common treatment used for NHL; when combined with Rituxan it is referred to as R-CHOP and is a standard treatment option for NHL.

R-CHOP consists of the following drugs:

  • Rituximab (Rituxan) Rituxan is a monoclonal antibody that has been designed to recognize and bind to B-cells. The binding of Rituxan stimulates the immune system to attack the B-cells and may also be involved in the direct killing or disabling of the B-cell.
  • Cyclophosphamide (Cytoxan) is a chemotherapy drug tht targets the DNA of cancer cells and signals them to stop dividing.
  • Doxorubicin hydrochloride (Adriamycin) is a chemotherapy drug that blocks an enzyme cancer cells need to grow and reproduce.
  • Vincristine (Oncovin, Vincasar, Vincrex) Vincristine is an alkaloid chemotherapy drug and is a vesicant, meaning it can damage tissues that it comes in contact with.

· Prednisolone a corticosteroid oral medication that works with your immune system to help reduce inflammation.

How is R-CHOP administered?

R CHOP is given in “cycles.” Each cycle begins with intravenous doxorubicin, vincristine and cyclophosphamide and is followed by oral prednisolone. Depending on the type of NHL patients will receive 4-8 cycles of R-CHOP. Cycles are typically administered every 21 days unless patients are receiving “dose dense” R-CHOP. Dose-dense R-CHOP is given every 14 days and is supported with a white blood cell growth factor to prevent low white blood counts, infection and fever.

Before each treatment a blood test is performed to check the white blood cell count and determine if the liver and kidneys are functioning well enough. If they’re not, the doctor may need to adjust the treatment.

What are the side effects of R-CHOP chemotherapy?

Chemotherapy is directed at killing or eradicating cancer cells. Unfortunately, cancer treatments may also damage normal, healthy cells that are not affected by the cancer. The result of this damage is a complication, or side effect, of treatment. Side effects occur because most cancer treatments cannot distinguish between cancer cells and normal, healthy cells. The main side effects of R-CHOP include the following. The most important side effect to understand is neutropenia or a low white blood count.

Caring for Yourself During Chemotherapy

Common Side Effects Include:

  • irritation around the intravenous or port site
  • red or pink urine for a few days due to doxorubicin
  • appetite changes
  • weight changes
  • indigestion
  • nausea
  • vomiting
  • fatigue
  • sleeping difficulties
  • low blood counts
  • allergic reactions

What Does the Research Show?

Four Cycles of R-CHOP can be Used to Treat Favorable Prognosis DLBCL

Standard therapy for young patients with favorable-prognosis diffuse large B-cell lymphoma (DLBCL) is six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) given every 21 days. (1)

New data from the FLYER clinical trial suggests that some patients can be spared two cycles of CHOP, with Rituxan still given over six cycles, and have excellent clinical outcomes, similar to those seen after the standard six cycles of R-CHOP.

In the FLYER clinical trial doctors from Germany treated 592 patients aged 18 to 60 years with “low risk” stage I/II DLBCL, with either six or four cycles of CHOP chemotherapy every 21 days plus the standard six cycles of Rituxan. “Low risk” was defined as an age-adjusted IPI of 0, age less than 60 and maximum disease diameter < 7.5 cm.

The 3-year progression-free survival with four cycles of CHOP was 96% compared to 94% seen with six cycles of CHOP, and overall survival was 99% and 98% respectively.

The authors concluded that low risk DLBCL patients can be spared two cycles of chemotherapy which reduces the average time on treatment from 126 to 84 days.

It’s important to understand that the results do not apply to the majority of patients with DLBCL and the results should not be applied to individuals over the age of 60.

Dose-Dense R-CHOP for Non-Hodgkin Lymphoma

Among patients with NHL supportive treatment with Neulasta® (pegfilgrastim) allows for the safe administration of the dose-dense treatment regimen R-CHOP-14 given every 14 days.

Dose-dense chemotherapy is a treatment approach where chemotherapy is administered as frequently as possible with the goal of delivering the greatest amount of chemotherapy over the shortest period of time, thereby delivering the maximum amount of chemotherapy drug to the cancer. Increasing the dose and frequency of chemotherapy administration appears to increase survival in some patients with non-Hodgkin’s lymphoma because dose-dense regimens may kill more cancer cells, but they also allow less time for bone marrow recovery and are associated with anemia (low red blood cell level) and neutropenia (low white blood cell level).

Neutropenia increases susceptibility to infection and can become a serious condition for several reasons: Many patients who develop neutropenia will require a delay in treatment or a dose reduction (both events can prevent them from receiving full benefits of treatment); patients who develop neutropenia may require hospitalization; and even minor infections can become life-threatening. Neulasta is a drug that is used to stimulate the production of immune cells in order to reduce or prevent neutropenia.

In order to evaluate the R-CHOP-14 researchers in Italy conducted a phase II clinical trial among 50 patients with DLBCL. Neulasta was given on the third day of each treatment cycle.

  • 92% of treatment cycles were delivered on time.
  • Severe (grade 4) neutropenia developed in 19% of treatment cycles and fever developed in 4% of treatment cycles.
  • 74% of patients experienced a complete remission following treatment.
  • After two years, overall survival was 68%.

The researchers conclude that a single dose of Neulasta in each treatment cycle allowed most patients with diffuse large B-cell lymphoma to receive their chemotherapy on time, with few cases of febrile neutropenia.

Six Cycles of R-CHOP-14 Remains Standard of Care for Elderly with Diffuse Large B-cell Lymphoma

Among elderly patients with diffuse large B-cell lymphoma, treatment with six cycles of Rituxan® and CHOP-14 produces better outcomes than CHOP-14 alone and may also produce better outcomes than eight cycles of Rituxan and CHOP-14.

To compare different approaches of administering CHOP with or without Rituxan in the treatment of elderly patients with diffuse large B-cell lymphoma, researchers in Germany conducted a study among more than 1,000 patients between the ages of 61 and 80 years.

Study participants were assigned to receive either six or eight cycles of CHOP administered every two weeks (CHOP-14). Half the patients also received Rituxan.

  • The addition of Rituxan improved outcomes compared to CHOP-14 alone.
  • Patients who received six cycles of Rituxan and CHOP-14 appeared to have the best overall survival.

The researchers concluded that six cycles of Rituxan and CHOP-14 appeared to produce the best outcomes in the treatment of elderly patients with diffuse large B-cell lymphoma. (3)


  1. American Society of Hematology (ASH) 2018. Presented December 2, 2018. Abstract 781.
  2. Pfreundschuh M, Kloess M, Zeynalova S, et al. Six vs. eight cycles of bi-weekly CHOP-14 with or without rituximab for elderly patients with diffuse large B-cell lymphoma (DLBCL): Results of the completed RICOVER-60 trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL).Blood. 2006;108;64a. Abstract 205.
  3. Brusamolino E, Rusconi C, Montalbetti et al. Dose-Dense R-CHOP-14 Supported by Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma: A Phase II Study of Feasibility and Toxicity. Haematologica. 2006;91:496-502.

Ibrutinib and Rituximab for Untreated CLL: ‘Practice Changing’

The combination of ibrutinib (Imbruvica, Pharmacyclics/Janssen) and rituximab (Rituxan, Roche/Genentech) beat the current gold standard of fludarabine, cyclophosphamide, and rituximab (FCR) for young, fit patients with untreated chronic lymphocytic leukemia (CLL) in a large trial funded by the National Cancer Institute (NCI).

Ibrutinib plus rituximab showed superior progression-free survival (PFS) and overall survival (OS) compared with FCR, and was also less toxic.

Tait D. Shanafelt, MD

These results from the E1912 study were presented here at the American Society of Hematology (ASH) 2018 Annual Meeting.

“These findings have immediate practice-changing implications and establish ibrutinib as the single most effective first-line therapy for patients with CLL,” lead author Tait D. Shanafelt, MD, from Stanford University, California, told Medscape Medical News.

“These definitive results show why large trials like this that test new therapies in an effort to achieve clinically meaningful benefit for patients are so important,” said Richard F. Little, MD, of the Cancer Therapy Evaluation Program at NCI in a statement.

Shifting Landscape

How these new findings fit alongside other recent results with ibrutinib in CLL is now a matter for consideration.

As reported by Medscape Medical News, data from another large NCI-sponsored trial, the ALLIANCE study, also presented at ASH, showed that ibrutinib alone was superior to the combination of bendamustine-rituximab in elderly patients ≥ 65 years of age with CLL. The investigators concluded that ibrutinib alone is appropriate as initial treatment of CLL in this patient population.

Additionally, results from an industry-sponsored study, the phase 3 iLLUMINATE trial — also presented at ASH (abstract 691) and submitted for approval of an additional indication — showed that the combination of ibrutinib and obinutuzumab (Gazyva, Roche/Genentech) provided a 77% reduction in risk of progression or death compared with chlorambucil and obinutuzumab (HR: 0.23; 95% CI: 0.15 – 0.37; P < .0001).

Aaron T. Gerds, MD

So three trials presented at the meeting suggest, in turn, that ibrutinib alone, ibrutinib plus rituximab, or ibrutinib plus obinutuzumab, should be the new standard for CLL. How are clinicians to choose between these regimens when treating patients with CLL?

“This is an embarrassment of riches,” commented Aaron T. Gerds, MD, of the Cleveland Clinic Taussig Cancer Institute, Ohio, who moderated an ASH press briefing during which the new results were discussed.

Ultimately, clinicians will have to weigh all the factors before deciding on the choices before them, he observed.

He also said that E1912 and ALLIANCE, large cooperative group studies, are important and unbiased, adding they are trials that industry is not likely to conduct. The iLLUMINATE study is industry sponsored and supports a US Food and Drug Administration (FDA) label — another way to pursue a treatment option, he pointed out.

Shanafelt pointed out although the E1912 study is not industry sponsored, it is registered with and has endpoints approved by the FDA. The study met all its endpoints, he noted, and hopes this new partnership between the cooperative groups and the FDA will get a nod for non-industry sponsored treatment options.

With ibrutinib approved as a single agent to treat newly diagnosed CLL, the E1912 study is the first trial in younger patients in which an ibrutinib regimen (ibrutinib plus rituximab) was compared with the gold-standard FCR regimen, and shows that for most patients an ibrutinib regimen should be preferred, lead author Jennifer A. Woyach, MD, of the ALLIANCE study, told Medscape Medical News.

“With these data it is probably appropriate to treat patients with either ibrutinib or the combination of ibrutinib and rituximab,” said Woyach, who is at Ohio State University Comprehensive Cancer, Columbus.

After the ASH meeting, practicing clinicians are likely to offer ibrutinib monotherapy first-line to treatment-naive CLL patients, commented Kanti R. Rai, MD, from the Feinstein Institute of Medical Research at Hofstra/Northwell, Hempstead, New York.

“It is a game changer,” he said and added that physicians are experienced with and comfortable using ibrutinib.

Rai believes data from the ALLIANCE study are more likely to inform clinical practice and ibrutinib monotherapy will be the standard in treatment-naive CLL. “Physicians, patients, and society have become sensitive to the cost of therapy, and with single-agent ibrutinib one is likely to avoid unnecessary expense,” he said.

“The age group difference [younger versus older] between E1912 and ALLIANCE is not likely to be critical,” Rai observed.

“We do not know for sure whether the data from ibrutinib-rituximab versus ibrutinib in older patients [ALLIANCE population] is generalizable to the entire CLL population, and I do not believe this comparison will ever be repeated in younger patients, so I think it is probably reasonable to choose either ibrutinib alone or in combination with rituximab in younger patients,” Woyach told Medscape Medical News.

Shanafelt indicated that the ongoing FLAIR trial is likely to provide a more definitive answer. FLAIR, which is enrolling patients with treatment-naive CLL aged 18 to 75 years, is evaluating four treatment regimens: FCR, ibrutinib-rituximab, ibrutinib-venetoclax, and ibrutinib alone.

Both Rai and Woyach predict that FCR will be used less but is appropriate for certain patients, such as those with mutated IGVH disease (low risk). “Long-term data from the FCR studies shows that a proportion of low-risk patients have the potential for very long-term remission and even cure. We will have to see with long-term follow-up from the E1912 study whether ibrutinib-rituximab is superior to FCR in IGVH mutated patients because that is not clear at this time,” Woyach said.

Shanafelt told Medscape Medical News that both E1912 and ALLIANCE are cooperative group studies and were designed simultaneously prior to the approval of ibrutinib (in 2014). E1912 was conducted in patients ≤ 70 years of age and ALLIANCE in those ≥ 65 years of age. “There was an intentional overlap because some patients have robust health and can tolerate FCR,” he said. “Both trials met their endpoint at the same time and based on the age category, ibrutinib-based therapy is the most effective compared with the best historic regimens,” he said.

“For all comers independent of age, ibrutinib-based treatment is the standard of care based on data from the two studies,” Shanafelt told Medscape Medical News.

The E1912 Study Results

The E1912 trial was a randomized phase 3 study that enrolled 529 patients (2:1) to ibrutinib plus rituximab (n = 354) or standard FCR therapy (n = 175). Patients enrolled were ≤ 70 years of age and those with 17p deletion were excluded because of poor disease response to FCR.

Patients treated with the combination of ibrutinib and rituximab received ibrutinib daily on days 1-28 for each cycle until disease progression or unacceptable toxicity. Rituximab was given in cycles 1-7. Patients in the FCR group were given the drugs over 6 cycles, as is typical in clinical practice.

Median age of patients was 58 years and 41% were ≥ 60 years; 75% of patients had IGVH unmutated disease.

Results were presented for the first interim analysis performed September 2018. Median follow-up was 33.4 months.

For the primary endpoint of PFS, the combination of ibrutinib and rituximab was associated with a 65% reduced risk for progression or death (hazard ratio [HR], 0.35; 95% CI, 0.22 – 0.5; P < .00001). Three-year PFS was 89% for the ibrutinib-rituximab combination and 73% for FCR.

OS was also superior for the combination of ibrutinib and rituximab (HR, 0.17; 95% CI, 0.05 – 0.54; P < .0003).

The superiority of the combination of ibrutinib and rituximab was seen regardless of age, performance status, disease stage, or presence or absence of del11q23. The superiority was also established for IGVH unmutated but not IGVH mutated disease.

Grade 3/4 treatment-related adverse events were reported for 58% and 72% of patients receiving the ibrutinib regimen and FCR, respectively. Compared with ibrutinib plus rituximab, FCR was associated with a significantly higher incidence of grade 3/4 neutropenia (22.7% vs 43.7%), anemia (2.6% vs 12.0%), thrombocytopenia (2.9% vs 13.9%), and infectious complications (7.1% vs 19.0%).

Study evaluates bendamustine and rituximab as front-line therapy for CLL

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is still the standard of care for physically fit patients with advanced chronic lymphocytic leukaemia (CLL), a trial has shown.

The international, open-label, randomized, phase III, non-inferiority study compared the efficacy and safety of the standard combination treatment with the bendamustine plus rituximab regimen.

A total of 688 treatment-naive, physically fit patients with CLL without del(17p) were recruited. Of the 564 patients who met the inclusion criteria, 561 were included in the intention-to-treat population. The patients were randomized to receive either standard therapy (n=282) or bendamustine plus rituximab (n=279). The patients were followed up at a median observation time of 37.1 months

Results showed that median progression-free survival for patients receiving fludarabine, cyclophosphamide and rituximab was 55.2 months, compared with 37.1 months for those receiving bendamustine and rituximab.

The null hypothesis for the corresponding non-inferiority hypothesis was not rejected.

The bendamustine and rituximab regimen was associated with less toxicity. More patients in the fludarabine, cyclophosphamide and rituximab group experienced severe neutropenia and infections compared to the other treatment group.

Rituximab May Be Helpful in Graves’ Orbitopathy

ompared to IV methylprednisolone for Graves’ orbitopathy, rituximab offers a number of advantages, Italian researchers say.

Dr. Mario Salvi told Reuters Health by email, “In this study the unexpected findings were that Graves’ orbitopathy after rituximab therapy does not relapse, when compared to a relapse rate of about 20-25% after standard treatment with steroids, observed after discontinuation of intravenous methylprednisolone.”

In a December 15th online paper in the Journal of Clinical Endocrinology & Metabolism, Dr. Salvi of the University of Milan and colleagues report on 31 patients randomized to IV methylprednisolone 7.5 mg or rituximab 500 g or 2000 g (i.e., 1000 g twice).

The clinical activity score fell with both treatments, but results with rituximab were significantly better at 16, 20 and 24 weeks. This was the case with both 2000 g and 500 g, with no significant difference between them.

In addition, at 24 weeks all rituximab patients had improved, compared to 69% of those in the methylprednisolone group. Motility scores in both left and right eyes were also better at 52 weeks. No disease reactivation was seen in the rituximab group, but five patients in the methylprednisolone group relapsed.

At 76 weeks, 12 of the 16 methylprednisolone patients had undergone rehabilitative surgical procedures, significantly more than 5 of the 15 patients given rituximab.

The results of this trial, say the investigators, confirm preliminary reports of a better therapeutic outcome with rituximab.
Dr. Salvi observed, “One single 500 mg dose of rituximab is as effective as 1000 mg twice in active Graves’ orbitopathy, suggesting that lower doses of this drug might be employed in this disease with the advantage of a lower risk for potential side effects and a lower therapeutic cost.”

“We, at the moment, recommend rituximab to be used in specialized centers for the care of Graves’ orbitopathy,” he concluded.

SOURCE: http://bit.ly/1Bl6Cdc

J Clin Endocrinol Metab 2014.

Rituximab outperformed steroids in Graves’ ophthalmopathy.

Despite data presented earlier at the American Thyroid Association Annual Meeting showing that rituximab was not effective in treating Graves’ ophthalmopathy, another presenter here said that the drug does improve disease state when compared with methylprednisolone.

“Response to rituximab was as high as 93%, compared to 69% observed after IV steroid,”Mario Salvi, MD, from the University of Milan in Italy, said. “Preliminary evidence of NOSPECS class 2 signs shows improvement after rituximab.”

Similar to the study presented earlier at the meeting, Salvi said the primary endpoint was a change of two or more points in the clinical activity score (CAS) at 24 weeks. Secondary endpoint was a reduction of disease severity by at least two NOSPECS classes.

Inclusion criteria included euthyroid for at least 6 to 8 weeks and affected by active Graves’ ophthalmopathy. Any previous steroid treatments had to be stopped at least 3 months before study inclusion.

Patients were randomly assigned to IV methylprednisolone (n=16; mean age, 50.4 years) or rituximab (Rituxan, Genentech; n=16; mean age, 51.9 years). In both groups, six patients had received previous steroid treatment. Originally, Salvi said, patients in the rituximab group were receiving 1,000 mg in two doses, but after two adverse reactions, they lowered the dosage to 500 mg. There was no difference between these two treatment dosages at 24 weeks.

At 12 weeks, the difference between the two groups was not significant, but at 24 weeks, 93% of patients in the rituximab group improved, as compared with 69% of the steroid group (P<.02).

“Rituximab was more effective than IV methyprednisolone in inactivating Graves’ orbitopathy, as assessed at 24 weeks,” Salvi said. “Graves’ orbitopathy remained invariably inactive after rituximab during follow-up.”

The researchers are confident in the response seen from methylprednisolone as it is as high as seen in recently published studies, Salvi said.

These results were preliminary and final analysis is expected shortly, he added.



Kenneth D. Burman

·         Both of the studies and each of the investigators did an excellent job in performing their studies. These studies are complex as it is difficult to recruit patients and to monitor them closely.

My initial impression is that the studies were designed differently. The Mayo Clinic study had rituximab as the active agent vs. placebo as the control, whereas the Italian study had rituximab as the active agent vs. intravenous steroids as an active control.

The doses of rituximab were also different. Salvi reduced the dose of rituximab mid-study and the lower dose was 500 mg/day vs. a total of 2,000 mg/day earlier in the study; the Mayo Clinic study used 2,000 mg. Salvi, et al suggested the lower dose was equally efficacious, but this needs to be explored further.

The major controversy relates to the patient population studied and whether the patients had received previous therapy, how recently this therapy had been given, the extent of therapy and the duration of disease. Stan, et al noted that about two-thirds of their patients did not receive treatment prior to the rituximab treatment, while Salvi, et al noted that six patients in each arm of their study had steroid treatment, but not within 3 months of the study.

Salvi, et al did indicate that their patients had progressive disease, which can defined by various scales. The CAS score, which was the sole measure in Salvi’s study, takes into account a multitude of factors. Stan, et al asserted that 24 of his 25 patients were classified as progressive as well. If the disease is progressive and treated early, the effect of immunomudulatory treatment is expected to be more efficacious. It is difficult to know with certainty if both studies analyzed patients at similar time points in the progression of ophthalmopathy.

Rituximab is not approved by the FDA for the treatment of Graves’ ophthalmopathy, The question now arises whether rituximab is effective in the treatment of progressive Graves’ ophthalmopathy given the apparent different results in these two clinical trials. Perhaps, the most appropriate advice is to refer these patients to large, tertiary medical centers that have extensive experience in treating patients with progressive Graves’ ophthalmopathy. Given that most physicians treating Graves’ ophthalmopathy are not experienced with using rituximab, and also give these conflicting results, it seems most prudent to not advise individual physicians to consider using rituximab therapy in this context outside of a tertiary medical center or a clinical trial.

o    Kenneth D. Burman, MD

o    Chief of the Endocrine Section at Washington Hospital Center 
Professor of Medicine 
Georgetown University

 Soure: Endocrine Today

What is Radioimmunotherapy (RIT) Treatment of NHL?

Radioimmunotherapy (RIT) is a type of targeted therapy that delivers radiation directly to cancer cells. It combines a monoclonal antibody—a type of protein that recognizes and binds to certain parts of cancer cells—with radioactive material. When the monoclonal antibody binds to the cancer cell, the radiation kills the cell.

Currently, RIT is used for the treatment of B-cell non-Hodgkin lymphomas (see examples below). RIT is also being evaluated for the treatment of other types of cancer, including prostate cancer and glioblastoma.

RIT is given on an outpatient basis, is generally completed in 10 days (as opposed to the longer duration of conventional chemotherapy), and avoids many of the side effects of chemotherapy. Because RIT may result in a temporary reduction in blood cell counts, patients typically need to have their blood cell levels monitored after treatment.

Examples of RIT

Zevalin® (ibritumomab tiuxetan): Zevalin therapy combines the monoclonal antibody Rituxan® (rituximab) with Zevalin, which is comprised of an anti-CD20 monoclonal antibody and Yttrium-90, a radioisotope that delivers the radiation. When injected into the body, Zevalin attaches to a protein (CD20) found only on the surface of B-lymphocytes, such as cancerous B-cells found in many forms of non-Hodgkin’s lymphoma. The radioactivity that is spontaneously emitted targets the B-cell and destroys it. This approach protects healthy tissue.  To learn more about Zevalin and view stories from other patients living with follicular lymphoma go to www.Zevalin.com. To locate a Zevalin-experienced oncologist click here.

Bexxar® (tositumomab and iodine I 131 tositumomab): Bexxar also targets B lymphocytes, and is comprised of an anti-CD20 monoclonal antibody and radioactive iodine 131. Bexxar is used for the treatment of certain patients with CD20-positive relapsed or refractory non-Hodgkin lymphoma.

Zevalin and Advanced Follicular Lymphoma

Researchers conducted a study that included 414 patients with CD20-positive stage III or IV follicular lymphoma who achieved a complete or partial response after first-line induction treatment. Patients were randomly assigned to receive Zevalin or no further treatment.

After a median follow-up of 3.5 years, the results indicated that Zevalin significantly prolonged median progression-free survival (PFS) in all patients, regardless of whether they had achieved a partial or complete response. Median PFS in patients treated with Zevalin was 36.5 months, compared to 13.3 months for patients in the control group. For patients who achieved a partial response after induction treatment, those who received Zevalin had a median PFS of 29.3 months compared to 6.2 months for those in the control group. Among patients who achieved complete response after induction, those who received Zevalin had a median PFS of 53.9 months compared to 29.5 months in the control group. What’s more, 77 percent of patients who experienced a partial response after induction converted to a complete response, which resulted in a final complete response rate of 87 percent.

The researchers concluded that Zevalin significantly prolonged PFS and resulted in a high conversion rate from partial to complete response, regardless of the type of first-line induction treatment.


Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. Journal of Clinical Oncology. 2008; 26: 5156-5164.


Source: cancerconnect.com

Autologous and Allogeneic Stem-Cell Transplantation for Transformed Follicular Lymphoma: A Report of the Canadian Blood and Marrow Transplant Group.


Purpose To determine whether autologous (auto) or allogeneic (allo) stem-cell transplantation (SCT) improves outcome in patients with transformed follicular lymphoma compared with rituximab-containing chemotherapy alone.

Patients and Methods This was a multicenter cohort study of patients with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patient, treatment, and outcome data were collected from each transplantation center and combined for analysis. A separate control group was composed of patients with transformation treated with rituximab-containing chemotherapy but not SCT. The primary end point was overall survival (OS) after transformation.

Results One hundred seventy-two patients were identified: 22 (13%) treated with alloSCT, 97 (56%) with autoSCT, and 53 (31%) with rituximab-containing chemotherapy. Five-year OS after transformation was 46% for patients treated with alloSCT, 65% with autoSCT, and 61% with rituximab-containing chemotherapy (P = .24). Five-year progression-free survival (PFS) after transformation was 46% for those treated with alloSCT, 55% with autoSCT, and 40% with rituximab-containing chemotherapy (P = .12). In multivariate analysis, patients treated with autoSCT had improved OS compared with those who received rituximab-containing chemotherapy (hazard ratio [HR], 0.13; 95% CI, 0.05 to 0.34; P < .001). On the other hand, there was no OS difference between those treated with alloSCT and rituximab-containing chemotherapy (HR, 0.44; 95% CI, 0.16 to 1.24; P = .12). OS and PFS after SCT were similar between those treated with autoSCT and alloSCT. Five-year transplantation-related mortality was 23% for those treated with alloSCT and 5% for autoSCT.

Conclusion Patients undergoing autoSCT had better outcomes than those treated with rituximab-containing chemotherapy alone. AlloSCT did not improve outcome compared with rituximab-containing chemotherapy and was associated with clinically significant toxicity.

Source: JCO



Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial.

Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas.
METHODS: We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335.
FINDINGS: 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69.5 months [26.1 to not yet reached] vs 31.2 months [15.2-65.7]; hazard ratio 0.58, 95% CI 0.44-0.74; p<0.0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved >/=3 cycles; p<0.0001), haematological toxicity (77 [30%] vs 173 [68%]; p<0.0001), infections (96 [37%] vs 127 [50%]); p=0.0025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0.0001), and stomatitis (16 [6%] vs 47 [19%]; p<0.0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 [16%] vs 23 [9%]; p=0.024).
INTERPRETATION: In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects.

Source: Lancet.