Treatment Options Template

Traditionally, advanced follicular lymphoma was treated with traditional chemotherapy regimens, either CHOP or CVP, which could induce remission but had little effect on overall survival. The discovery of the first monoclonal antibody, rituximab, altered treatment protocols fundamentally, causing much longer and more reliable responses to treatment. Relapsing follicular lymphoma may be treated with alternative drug regimens or an allogeneic or autologous stem-cell transplant. Several advanced new drugs show promise in treating the disease.

1. Watch & Wait (W&W)

2. First-Line Treatment for Follicular Lymphoma

3. Consolidation for Follicular Lymphoma

4. Maintenance for Follicular Lymphoma

5. Second-Line (and Subsequent) Treatment for Follicular Lymphoma

6. Transformation

7. New Therapies

Novel Antibodies -- The TRAIL-R1 receptor is targeted by mapatumumab.

Protein Inhibitors and Enzyme Inhibitors -- New drugs that may inhibit the Bcl-2 protein include navitoclax.

Further Reading

See John Gribben, "How I Treat Indolent Lymphoma," Blood (2007).

Other Lymphomas

For mantle cell lymphoma, see Michele Ghielmini and Emanuele Zucca, "How I Treat Mantle Cell Lymphoma," Blood (2009). For diffuse large B-cell lymphoma (DLBCL), see James Armitage, "How I Treat Patients with Diffuse Large B-Cell Lymphoma," Blood (2007); and Michael Pfreundschuh, "How I Treat Elderly Patients with Diffuse Large B-Cell Lymphoma," Blood (2010).

Why Median Survival Times Aren't (That) Helpful

The median is one of the most common statistical tools used in clinical research reports in oncology. They're also, from the patient's perspective, not as helpful as they seem at first glance. It's very important to be realistic about what statistics mean, especially when our lives are on the line. This doesn't always mean being pessimistic about the data. Rather, it means understanding what the data tells us -- and, equally importantly, what it doesn't tell us.

A median is, briefly, one type of average. There are three types of averages: mean (the most common type outside of clinical research), mode, and median. In short, the median is the point at which 50% of a sample have a particular attribute, or have accomplished some particular task. For instance, a country's median income is a dollar figure which half of the people earn less than, and half of the people earn more than. In cancer trials, median survival means the point at which half the patients recruited into the trial have died. And that's all it means -- it doesn't say when the 50% who died did so, or how long the other 50% are likely to live.

New Clinical Trial Information: Imetelstat Sodium Telemerase Inhibitor

Trial Information: 45 young patients will be recruited for a Phase I study of the new telemerase inhibitor imetelstat. Patients must be under 21 years old and have any solid tumor or lymphoma cancer, except for brain tumors or metastases. They must have relapsed or been resistant (refractory) to previous retreatment.

New Clinical Trial Information: Lucatumumab + Bendamustine

Trial Information: 50 patients are being recruited for a Phase I trial of the new anti-CD40 monoclonal antibody lucatumumab (aka HCD122). Patients must have follicular lymphoma and have become resistant to rituximab following previous therapy. Patients will be given combination therapy of lucatumumab with bendamustine, a relatively new alkylating agent.

Urine Therapy for Follicular Lymphoma?

And I thought I'd heard (almost) everything. John Bettens says that he has kept his follicular lymphoma at bay for going on three years now, by drinking one cup of his own urine every day. Maybe. I honestly do hope that Bettens's tumours continue to shrink, and disappear, and stay that way. But I also have to say that I genuinely can't see how that would be related to urine.

The statistical record shows that around one in four or five lymphoma patients experiences meaningful regression (shrinking) of tumours, and most of the rest of follicular lymphoma patients still have a very slow disease course. This makes it a very ripe field for misleading anecdotal evidence.

How Clinical Trials Work

A clinical trial is the standard tool of scientific, evidence-based medicine for determining the safety and effectiveness of new drugs and drug combinations, including for cancer therapy.

The basic appeal of clinical trials for patients is the ability to gain access to potentially powerful new drugs which are not yet approved and may be unavailable in hospitals or clinics for years. However, consent to participate in a clinical trial should never be given lightly. As a patient, you need to be aware of the objectives of the trial, basic information about the drug, how likely the trial's researchers believe you might benefit from what they want to put into your body, and what the potential side effects and negative consequences of treatment might be.

Drug Information: Bendamustine

Also known as: Treanda

Canadian Status: Bendamustine is not yet approved in Canada for the treatment of follicular lymphoma. However, it is currently being used in several Canadian clinical trials, including a comparison of rituximab + bendamustine with R-CHOP/R-CVP.

New Drug Information: Lucatumumab Anti-CD40 Monoclonal Antibody

Also known as: HCD122

Drug Information: Lucatumumab is one of several experimental anti-CD40 monoclonal antibodies. CD40 is a cellular surface protein involved in immune system signaling, which is present on cancerous B cells. The drug's developer, Novartis, believes that it both blocks proliferation of malignant cells and attracts other immune system cells to attack the cancer. It is given intravenously on a weekly basis for multi-week treatment cycles.

95% of Statistics are Bogus (Including This One)

My own Statistics page still languishes in its unstarted state, but a new article in Science News manages to present, more or less in layman's terms, precisely the sorts of problems that I wanted to highlight for readers here. So in the meantime, it's a useful starting point.

Tom Siegfried explains very well that the scientific method and statistical analysis are not necessarily natural bed-partners, and that even the games we play to make statistics seem "reliable" can end up, in certain cases, actually making them more misleading. Most of this will be old news to people with stats training, but it's still a good refresher. There's also a section specifically on the problems inherent in clinical trials:

Statistical problems also afflict the “gold standard” for medical research, the randomized, controlled clinical trials that test drugs for their ability to cure or their power to harm. Such trials assign patients at random to receive either the substance being tested or a placebo, typically a sugar pill; random selection supposedly guarantees that patients’ personal characteristics won’t bias the choice of who gets the actual treatment. But in practice, selection biases may still occur, Vance Berger and Sherri Weinstein noted in 2004 in Controlled Clinical Trials. “Some of the benefits ascribed to randomization, for example that it eliminates all selection bias, can better be described as fantasy than reality,” they wrote.

Clinical Trial Information: RO4929097 Gamma-Secretase Inhibitor

Trial Information: 40 patients are being recruited for a Phase I study of the experimental new gamma-secretase inhibitor RO4929097 in combination with capecitabine, an oral DNA synthesis inhibitor already used in colon cancer and breast cancer. Eligible patients include those with any metastatic solid tumor cancer or lymphoma.

Clinical Trial Information: AEG35156

Trial Information: 51 patients are being recruited for a Phase I/II trial of the XIAP antisense AEG35156 in indolent lymphomas (including follicular lymphoma) and chronic lymphocytic leukemia (CLL). Patients must meet criteria for third-line treatment (or beyond) to enter the trial.

New Clinical Trial Information: GA101 Monotherapy

Trial Information: 180 patients with relapsed indolent lymphoma, including follicular lymphoma, will be recruited to test GA101 (aka RO5072759) monotherapy. Although this is a Phase II trial, patients will be randomized to receive either GA101 monotherapy or rituximab monotherapy.

New Drug Information: Galiximab

Drug Information: Galiximab is a chimeric human-macaque anti-CD80 monoclonal antibody which targets B-cells, including malignant cells. Blocking this site with antibodies appears to produce a range of anti-cancer effects. It is taken intravenously, weekly for four weeks.

New Drug Information: Bortezomib

Also known as: Velcade

Drug Information: Bortezomib is a proteasome inhibitor, a type of drug which targets structures inside the cell responsible for breaking down proteins. It has been theorized that cancerous cells are particularly vulnerable to this sort of induced dysfunction. It is typically given twice-weekly; weekly regimens were attempted in trials, and had fewer side effects but limited response rates.

New Drug Information: Ocrelizumab

Drug Information: Ocrelizumab is a fully human anti-CD20 monoclonal antibody which in preclinical studies was more powerful than rituximab. It is taken intravenously.

New Drug Information: Vorinostat Histone Deacetylase Inhibitor

Also known as: Zolinza, suberoylanilide hydroxamic acid


Drug Information: Vorinostat is a new histone deacetylase inhibitor, a class of drugs that block specific enzymes and appear to have some role in suppressing malignant activity on the intracellular level. In the trial setting for indolent lymphoma, vorinostat has been taken orally, daily.

Watch & Wait in Follicular Lymphoma

Follicular lymphoma is indolent (slow-growing), and (at least for the moment) incurable. For this reason, studies have shown in the past that there is no benefit to beginning immediate treatment per se. The exception is in early, localized disease, when chemotherapy and radiation treatment may be able to effect a cure. Most patients have advanced (Stage III or Stage IV) disease at diagnosis, but have no symptoms (are "asymptomatic") other than swollen lymph nodes.

That doesn't mean "watch & wait" is a comforting strategy for patients, though. Quite the contrary -- "watch & worry," as the less formal title for this strategy goes, can be a time of great stress and anxiety. For this reason, it's important to know the arguments for and against watch and wait, to determine whether this really is beneficial for you and your loved one.

How Watch & Wait (W&W) Works

Nervous patients understandably put the emphasis on the "wait" part. Oncologists tend to put the emphasis on the "watch" part. During watch and wait, patients check in with their physician on an established schedule, such as every three tests. Palpable (feelable) lymph nodes are examined, blood counts are taken, and standard scans (such as CT scans) are ordered, and the results are compared with those of the previous examination. For most patients, follicular lymphoma grows slowly, and these checkups allow the doctor and patient to monitor the progress of the disease. Eventually, usually when symptoms appear (criteria are discussed in further detail below), watch and wait ends and treatment begins.

Who is Eligible for PET Scans in Ontario?

When government insistence on cutting costs runs up against increasingly technologically advanced modern medicine, the resulting tangle of public health regulation can be just as complicated and unhelpful as the convoluted policies of any private health insurance company. An excellent example of this is the current situation for Ontario residents seeking PET scans. I'm providing this page as a guide for Ontario residents and an illustration of medical rationing gone mad.

PET scans, including combined PET/CT scans (the current standard of care), are an important tool in detecting, staging, and restaging many types of cancer, including lymphoma. PET scans may use a mildly radioactive tracer molecule, like FDG, which is absorbed in the body like sugar. Cancerous cells tend to demand more than their fair share of sugar, so they light up on the PET scan. Or they do in some provinces, anyways. According to the Canadian Agency for Drugs and Technologies in Health (CADTH), Quebec, with a population of about 8 million, conducts 21,000 PET scans a year. Ontario, with a population in excess of 13 million, funded just 2000 PET scans a year, although that number is probably now increasing substantially thanks to new funding provisions.

In the Ontario provincial healthcare system, there are several methods for qualifying for a PET scan from PET Scans Ontario. The bright side is, there's no waiting list. Unfortunately, that's because PET scans are strictly rationed. Only one of the criteria is directly relevant to lymphoma patients, and it includes only some lymphoma patients:

Clinical Trial Information: GA-101 and Bendamustine

Trial Information: This is a Phase III trial recruiting 360 Canadian and American patients with indolent lymphoma, including follicular lymphoma, who have been previously treated and are refractory to rituximab. Patients will be randomized to receive bendamustine monotherapy or bendamustine with GA-101 (B-G).

New Clinical Trial Information: Ofatumumab + Bendamustine

Trial Information: This is an international Phase III trial of ofatumumab. 338 patients with relapsed or refractory indolent lymphoma, including follicular lymphoma, will be randomized to receive either bendamustine monotherapy or ofatumumab plus bendamustine (O-B), in eight 21-day cycles.