Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.

Revlimid is an oral medication that can stop or slow the growth of cancerous myeloma cells within the bone marrow. It has been approved in combination with dexamethasone for multiple myeloma patients who have received at least one prior therapy. Revlimid has been associated with an increased risk of new cancers and the FDA recently made a safety announcement regarding the drug.[1]

Despite the increased risk of new cancers, Revlimid continues to be studied for its use as maintenance therapy in multiple myeloma. Three double-blind, phase 3, multi-center, randomized trials evaluated Revlimid maintenance therapy. Two studies randomly assigned patients to Revlimid or placebo after stem-cell transplantation. The third study included patients who were ineligible for stem-cell transplantation; these patients were randomly assigned to Revlimid or placebo after oral induction therapy. In all three studies, study-drug assignments were unblended early after Revlimid maintenance showed significant benefit.

In the first study, researchers assigned 614 patients under age 65 to Revlimid or placebo after transplantation.[2] They found that maintenance therapy with Revlimid improved progression-free survival, with a progression-free survival of 41 months in the Revlimid group compared to 23 months in the placebo group. After a median follow-up of 45 months, more than 70 percent of patients in both groups were alive at 4 years. There was an increased rate of new cancers in the Revlimid group, with 32 new cancers in the Revlimid group and 12 in the placebo group. However, the researchers concluded that the benefit of Revlimid outweighed the risk of new cancers.

In the second study, 460 patients age 71 or younger were randomly assigned to Revlimid or placebo after transplantation.[3] Patients in the Revlimid group had a significantly longer time to disease progression compared to those in the placebo group—the median time to progression was 46 months in the Revlimid group and 27 months in the placebo group. Patients in the Revlimid group experienced more grade 3 and 4 adverse events and 18 (8%) patients in the Revlimid group had second primary cancers, compared with 6 (3%) in the placebo group. A total of 35 patients who received Revlimid (15%) and 53 patients who received placebo (23%) died.

The third study involved patients who were ineligible for transplantation.[4] In this study, patients were randomly assigned to one of three groups:152 patients received oral melphalan-prednisone-Revlimid induction followed by Revlimid (MPR-R); 153 patients patients received oral melphalan-prednisone-Revlimid followed by placebo (MPR); and 154 patients received melphalan-prednisone followed by placebo (MP). The median progression-free survival was significantly longer with Revlimid maintenance therapy—the MPR-R group had a median progression-free survival of 31 months, compared to 14 months for the MPR group and 13 months for the MP group. The rate of new cancers was 7% with MPR-R, 7% with MPR, and 3% with MP.

In an accompanying editorial, Ashraf Badros notes that while Revlimid appears to offer benefit as maintenance therapy for multiple myeloma, it does come with risks, namely the increased risk of second primary cancers.[5] Furthermore, he questions whether progression-free survival is the optimal endpoint for maintenance therapy and whether it is the most cost-effective treatment.

References:

Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. To examine the link between infections and cancer, researchers performed a systematic analysis of the proportion of cancer cases attributable to infection in 2008. They used data on cancer incidence from the GLOBOCAN project along with epidemiological data regarding the causal effects of infection on cancer. The data included information on 27 types of cancer from 182 countries.

They found that of the 12.7 million new cancer cases that occurred worldwide in 2008, 16 percent—or roughly two million—were attributable to infections. The rate of infection-related cancer was about three times higher in developing countries. For example, 3.3 percent of cancers in Australia and New Zealand were infection related, whereas 32.7 percent of cancers in sub-Saharan Africa were attributable to infections. The four main infections associated with cancer were human papillomavirus, hepatitis C, hepatitis B, and Helicobacter pylori. These infections were responsible for approximately 1.9 million cancer cases in 2008, mainly gastric, liver, and cervical cancers.

Cervical cancer accounted for about half of the infection-related cancers in women. Liver and gastric cancers accounted for more than 80 percent of the infection-related cancers in men.  About 30 percent of infection-related cancers occurred in people younger than 50 years. It’s important to note that it takes decades of chronic infection before an infection progresses to cancer.

Based on the statistics, the researchers noted that approximately two million cancer cases each year might be preventable with better public health methods for preventing infection. In an accompanying editorial, Dr. Goodarz Danaei, an assistant professor of global health at Harvard School of Public Medicine in Boston, noted that vaccines for HPV and hepatitis B are effective and that increasing their availability should be a priority for higher risk countries.[2] He suggests that increasing vaccine coverage could reduce the global burden of cancer.

References:

Revlimid is an oral medication that can stop or slow the growth of cancerous myeloma cells within the bone marrow. It has been approved in combination with dexamethasone for multiple myeloma patients who have received at least one prior therapy. Revlimid has also been evaluated in combination with other agents for the initial treatment of patients with newly diagnosed myeloma.

Clinical trials have been ongoing since Revlimid was approved and new data indicates that newly diagnosed patients treated with Revlimid have an increased risk of developing acute myelogenous leukemia (AML), myelodysplastic syndromes, and Hodgkin’s lymphoma.

One analysis included three randomized trials in which patients with newly diagnosed multiple myeloma received initial chemotherapy or chemotherapy and blood-stem-cell transplantation followed by treatment with Revlimid or placebo. The FDA reports that there was nearly a three-fold increase in new cancers in the Revlimid group compared to the placebo group, with 65 second primary cancers among 824 Revlimid patients and 19 second primary cancers among 665 placebo patients. The median time from start of Revlimid to a diagnosis of a second primary malignancy was two years.

The safety information has been added to Revlimid’s label to provide up-to-date information to healthcare professionals. The patient information is also being updated.

The FDA has recommended that doctors consider both the potential benefit of Revlimid as well as the risk of new cancers when choosing to treat patients with the drug. Patients must be closely monitored for the development of new cancers.

Reference:

FDA Drug Safety Communication: Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies [FDA Safety Announcement]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm302939.htm

How does cancer treatment affect fertility in men?

Chemotherapy: Chemotherapy can temporarily—and in some cases, permanently—stop sperm production by the testes.[1] The extent to which chemotherapy affects sperm production depends on several factors, including the type and dose of chemotherapy.

Radiation: Radiation to the abdomen or pelvis can also reduce or eliminate sperm production by the testes.

Surgery: Surgery that involves the removal of both testicles (an option for some men with prostate cancer) eliminates sperm production, but other types of surgery can also affect a man’s fertility. Some types of pelvic surgery, for example, can change or eliminate ejaculation.

Options for preserving fertility in men

Although many men are able to conceive naturally after cancer treatment, others are not.

If possible, men should talk with their doctor about their future fertility before beginning cancer treatment. Some options for preserving fertility require that steps be taken before cancer treatment begins.

Sperm banking is the most well-established method of preserving fertility in men.[2] It involves the collection and storage of sperm, ideally before cancer treatment begins. The samples are kept frozen at a lab or sperm bank until they are needed. Sperm can be stored in this way for many years. After being thawed, the sperm can be used for intrauterine insemination (IUI) or in vitro fertilization (IVF). During IUI, sperm are placed directly into a woman’s uterus. During IVF, mature eggs are removed from a woman’s ovary and mixed with the sperm in the lab. Embryos that result from IVF can then be placed in a woman’s uterus or frozen for later use.

If a sample contains very few viable sperm (or if a man has already undergone cancer treatment and has a low sperm count), another approach may be used to fertilize an egg. Intracytoplasmic sperm injection (ICSI) requires only a small number of healthy sperm, along with mature eggs that have been collected from a woman’s ovary. A single sperm is injected directly into each egg. The embryos that develop can then be placed in a woman’s uterus or frozen for later use.

If it is not possible to collect sperm from ejaculate, it may in some cases be possible to collect sperm directly from the testicles. This approach is still investigational.

Finally, it may also be possible to modify some cancer treatments to minimize their effects on subsequent fertility. During radiation therapy, for example, it may be possible to shield the testes in order to preserve sperm production.

Pregnancy after cancer

In the event that your fertility is not affected by cancer treatment (or recovers quickly or unexpectedly), you and your partner should use birth control if you do not wish to have a child. If you are trying to conceive a child naturally, your doctor may advise you to wait for several months after treatment; this allows for the elimination of sperm that may have been damaged during treatment.

In general, the risk of birth defects in children born to cancer survivors appears to be similar to the risk in the general population.[3] If your cancer was due to a hereditary cancer syndrome, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer), your children may inherit the gene mutation responsible for your family’s increased risk of cancer. Talking with a genetic counselor may be helpful.

Other options for parenthood

Not all men have the luxury of being able to explore their reproductive options before beginning cancer treatment, and not all men will find a fertility preservation option that meets their needs. But there are still ways to become a parent. Discussion of other routes to parenthood may be a painful topic for men who want to father a child but cannot. But as cancer survivors consider how best to build their families, methods such as adoption are important options.

Adoption: Couples and individuals who wish to adopt have a range of options, including different types of domestic and international adoptions. You may wish to start by learning about the adoption laws in your state and by talking with other adoptive parents about the professionals and agencies they worked with. Before selecting an adoption agency, you may wish to talk with them about their attitudes toward placing a child with a cancer survivor. Many agencies will be receptive toward this, but it’s important to know before making a final decision.

Donor Sperm: Donor sperm is readily available from sperm banks and can be used for either intrauterine insemination or in vitro fertilization.

Individual decisions within a larger community

The decisions that you make about building a family (or about coming to terms with not building a family) will be intensely personal, but know that you are part of a larger community of patients and healthcare providers who are grappling with these issues.  To think about future parenthood is to think about life after cancer. For many people with cancer, planning for the future may provide the motivation needed to get through treatment.

More information?

Discuss with others…. http://cancerconnect.com/groups/young-adults/topics/fertility-after-cancer-treatment

Fertile Hope (www.fertilehope.org) provides a range of fertility resources for people with cancer.

References:

How does cancer treatment affect fertility in women?

Chemotherapy: Many chemotherapy drugs are toxic to the egg cells (oocytes) in the ovaries. If the number of remaining oocytes in the ovaries reaches a critically low point during treatment, women experience “acute ovarian failure.” This means that the ovaries stop functioning during or shortly after cancer treatment. If oocytes are lost during treatment but do not reach this critically low point, women are at risk for early menopause but may still be able to get pregnant for some time after treatment.

Radiation: Radiation to the pelvis can also destroy oocytes. Radiation to the pelvis can also affect uterine growth and blood flow, particularly if received before puberty.[1] A poorly developed uterus may make a woman more likely to have a miscarriage, or more likely to have a preterm or low-birthweight infant.

Surgery: Some cancers require surgical removal of the uterus, the ovaries, or both.

The effects of cancer treatment on fertility can vary substantially by age. Younger women, who have a larger pool of oocytes when they start cancer treatment, are more likely than older women to be able to get pregnant after treatment.[2]

Options for preserving fertility in women

If possible, women should talk with their doctor about their future fertility before beginning cancer treatment. Some options for preserving fertility require that steps be taken before cancer treatment begins.

One of the most established approaches for preserving fertility among female cancer patients is embryo freezing.[3] Before starting cancer treatment, a woman would be given hormones to stimulate the development of eggs in her ovaries. Mature eggs would be removed and fertilized with the sperm of her husband, partner or a sperm donor. The embryos that result from these fertilized eggs would be frozen for later use.

Although embryo freezing is an established approach to helping women become pregnant after cancer, there are downsides. A woman may not currently have a male partner and may be unwilling to use an anonymous sperm donor. It’s also important to be aware that embryo freezing takes approximately two weeks after the start of a woman’s period. If a woman needs to begin cancer treatment immediately, she may not be able to go through this process. Finally, this approach is only an option for women of childbearing age; stimulating the ovaries to produce mature eggs is not an option for girls who develop cancer during childhood.

Several other options are still in the experimental phase. One approach being explored is the freezing of unfertilized eggs.3 Once again, the ovaries would be stimulated to produce mature eggs before cancer treatment begins. The eggs would then be frozen without being fertilized by sperm. Currently, freezing unfertilized eggs is less likely to result in pregnancy than freezing embryos, largely because unfertilized eggs are less likely than embryos to survive the process of freezing and thawing. Nevertheless, it may be an option for women who do not have a male partner at the time of their cancer diagnosis, and it avoids the difficult issue of what to do with unused embryos.

Another promising but still experimental approach is to freeze all or a part of an ovary before cancer treatment.[4] After treatment, the ovarian tissue is implanted either back in the woman’s pelvis or in another location (such as under her skin). If this process is successful, the ovarian tissue will begin producing eggs. A safety concern with this approach is the possibility of reintroducing cancer cells along with the ovarian tissue, and the tissue will need to be carefully screened for cancer before it is transplanted.4

Finally, it may also be possible to modify some cancer treatments to minimize their effects on subsequent fertility. For example, shielding the ovaries during radiation, or moving the ovaries out of the radiation field, may protect them from the effects of radiation. Scientists are also exploring whether using drugs to suppress the activity of the ovaries during chemotherapy will make the ovaries less susceptible to damage by chemotherapy.[5] For women with certain types of cervical or ovarian cancer, fertility-preserving surgery may also be an option.[6] It’s important to understand that only specific subsets of patients will be candidates for these approaches, and that some of the methods are still in the early stages of evaluation.

Pregnancy after cancer

In addition to having concerns about their ability to get pregnant, women may have concerns about whether pregnancy after cancer treatment will be safe for themselves and their children. While there is a limited amount of information about these topics, the news is generally good.

The risk of cancer recurrence during or after pregnancy has been most studied in women with breast cancer, and these studies generally have reported that pregnancy does not increase the risk of breast cancer recurrence. [7] Many doctors, however, suggest waiting for a period of time after treatment before becoming pregnant. [8]

If chemotherapy or radiation therapy has damaged her heart or lungs, a woman may also have concerns about the strain that pregnancy will put on her body. Studies of breast cancer survivors suggest that long-term heart problems are uncommon after chemotherapy or radiation therapy, [9] but a woman may wish to talk with her doctor about her current health status and the likely effects of pregnancy.

Children born after their mother’s cancer treatment do not appear to be more likely than other children to have birth defects or cancer.[10] If a woman’s cancer was due to a hereditary cancer syndrome, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer), her child may inherit the gene mutation responsible for her family’s increased risk of cancer. Talking with a genetic counselor may help clarify the child’s risk.

When planning for pregnancy, be aware that some cancer treatments may cause you to have an early menopause even if your periods resume after treatment. Also be aware that you may be capable of conceiving even if your periods do not resume; continue to use birth control if you do not wish to become pregnant.

Other Options for Parenthood

Not all women have the luxury of being able to explore their reproductive options before beginning cancer treatment, and not all women will find a fertility preservation option that meets their needs. But there are still ways to become a parent. Discussion of other routes to parenthood may be a painful topic for women who want to become pregnant and cannot. But as cancer survivors consider how best to build their families, methods such as adoption are important options.

Adoption: Couples and individuals who wish to adopt have a range of options, including different types of domestic and international adoptions. You may wish to start by learning about the adoption laws in your state and by talking with other adoptive parents about the professionals and agencies they worked with. Before selecting an adoption agency, women may wish to talk with them about their attitudes toward placing a child with a cancer survivor. Many agencies will be receptive toward this, but it’s important to know before making a final decision.

Egg Donation: Women who still have a uterus may be able to become pregnant using an egg donated by another woman. Through in vitro fertilization, the donated egg would be fertilized by the cancer survivor’s male partner or a sperm donor, and implanted in her uterus. Alternatively, another couple may donate a frozen embryo that could be implanted in her uterus.

Gestational Carrier or Surrogate: Women who do not have a uterus, or who are otherwise unable to sustain a pregnancy, may be able to have another woman carry a pregnancy for them. If the cancer survivor has functioning ovaries, her own egg can be fertilized by her male partner’s sperm and transferred to the uterus of another woman. In this case, the woman who carries the pregnancy is known as a gestational carrier. If the cancer survivor does not have functioning ovaries, another woman can both donate an egg and carry the pregnancy. This is the arrangement traditionally known as surrogacy.

Individual Decisions Within a Larger Community

The decisions that you make about building a family (or about coming to terms with not building a family) will be intensely personal, but know that you are part of a larger community of patients and healthcare providers who are grappling with these issues.

To think about future parenthood is to think about life after cancer. For many people with cancer, planning for the future may provide the motivation needed to get through treatment.

More Information?

Discuss with others….. http://cancerconnect.com/groups/young-adults/topics/fertility-after-cancer-treatment

Fertile Hope (www.fertilehope.org) provides a range of fertility resources for people with cancer.

References:

A growing body of evidence suggests that aspirin may reduce the risk of several types of cancer, with particularly strong evidence for colorectal cancer. Not all studies have found a benefit, however, and any potential benefits of aspirin must be weighed against risks such as bleeding.

To further explore the relationships between daily aspirin and cancer, researchers conducted a combined analysis of 51 previous randomized trials.[1] The trials were originally designed to evaluate the effect of daily aspirin on outcomes such as heart disease, but information about cancer was also available.

• Daily aspirin reduced cancer deaths. After five years, aspirin users had a 37 percent reduction in risk of cancer death.
• Aspirin also reduced the likelihood of developing cancer. From three years onward, aspirin users had a 24 percent reduction in the risk of being diagnosed with cancer.
• As expected, aspirin carried a risk of major bleeding, but this risk appeared to diminish over time.

Another study published in the same issue of The Lancet evaluated the effect of daily aspirin on cancer metastasis (the spread of cancer from its original site to other parts of the body). The study focused on 987 people who were diagnosed with cancer while participating in one of five trials of aspirin use. Those who were taking aspirin were less likely to have metastatic cancer than those who were not taking aspirin.[2]

These results suggest that regular aspirin use may reduce cancer incidence and mortality, but concerns remain about the risks of regular aspirin use in healthy individuals. People who are considering using aspirin on a regular basis are advised to discuss the risks and benefits with their physician.

References:

Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.

Carfilzomib is a type of targeted drug known as a proteasome inhibitor. It has produced good results in patients with relapsed or refractory multiple myeloma, and is also being evaluated in patients with earlier-stage disease. Carfilzomib is taken orally (by mouth).

To evaluate carfilzomib among patients with newly diagnosed multiple myeloma, researchers conducted a Phase I/II clinical trial among 53 patients. All patients were treated with a combination of carfilzomib, Revlimid, and low-dose dexamethasone.

• 94 percent of patients had at least a partial response (a partial reduction in detectable cancer) after completing the first cycle of treatment.
• Responses continued to improve with additional treatment cycles. Among patients who had received at least 12 cycles of treatment, all had at least a very good partial response.
• After 9.5 months of follow-up, all of the patients were alive and only one had experienced a worsening (progression) of their cancer.

These results suggest that the combination of carfilzomib, Revlimid, and low-dose dexamethasone is active against newly diagnosed multiple myeloma. Carfilzomib will continue to be evaluated among patients with various stages of multiple myeloma.

Reference: Jakubowiak AJ, Dytfeld D, Jagannath S et al. Final results of a frontline Phase 1/2 study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in multiple myeloma (MM). Presented at the 53^rd ASH Annual Meeting and Exposition.San Diego,CA, December 10-13, 2011. Abstract 631.

Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.

High-dose cancer treatment followed by a stem cell transplant may be used in the treatment of several types of hematologic cancers, including multiple myeloma. Stem cell transplants may use the patient’s own stem cells that were collected prior to cancer treatment (an autologous transplant) or stem cells donated by another person (an allogeneic transplant).

For multiple myeloma patients who relapse after initial treatment with an autologous stem cell transplant, the effects of a second (salvage) autologous transplant have been uncertain. To explore this question, researchers conducted a study among 44 myeloma patients (median age of 54) who had relapsed and been treated with a second autologous stem cell transplant. The interval between the first and second transplant ranged from two to 78 months (median interval was 2.6 years).

Forty-one percent of patients received maintenance therapy after the second transplant.

• Roughly one-quarter of the patients experienced severe (grade 3 or worse) non-blood-related side effects. There was one treatment-related death.
• 11 percent of patients had a complete response or a near-complete response to salvage treatment, and 79% had a partial response.
• Median time to progression after salvage treatment was just over a year. Overall survival was 2.6 years.

These results suggest that for selected myeloma patients, treatment of a relapse with a second autologous stem cell transplant is an option.

Reference: Shah N, Ahmed F, Bashir Q et al. Durable remission with salvage second autotransplants in patients with multiple myeloma. Cancer. Early online publication November 15, 2011.

Multiple myeloma is a cancer of plasma cells. Plasma cells are a special type of white blood cell that are part of the body’s immune system. Plasma cells normally live in the bone marrow and make proteins, called antibodies, which circulate in the blood and help fight certain types of infections. Plasma cells also play a role in the maintenance of bone by secretion of a hormone called osteoclast activating factor, which causes the breakdown of bone. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine. These abnormal antibodies are referred to as paraproteins or monoclonal proteins in the blood (M proteins) or urine (Bence Jones protein).

Velcade is the first in a new class of anticancer agents known as proteasome inhibitors. It’s been shown to provide benefits in the treatment of multiple myeloma and mantle cell lymphoma.

The VISTA study is an international Phase III clinical trial. The study involved 655 previously untreated multiple myeloma patients who were ineligible for stem cell transplantation. Patients were assigned to receive treatment with melphalan and prednisone alone (MP) or in combination with Velcade (VMP). Patients have now been followed for five years.

• The addition of Velcade improved overall survival by more than 13 months: overall survival was 56.4 months among patients treated with VMP and 43.1 months among patients treated with MP.
• Neither treatment group had an increased risk of second cancers compared with the general population.

These results suggest that the addition of Velcade to melphalan and prednisone improves overall survival among patients with previously untreated multiple myeloma who are not eligible for stem cell transplantation.

Reference: San Miguel JF, Schlag R, Khuageva NK et al. Continued overall survival benefit after 5 years’ follow-up with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with previously untreated multiple myeloma, and no increased risk of second primary malignancies: final results of the phase 3 VISTA trial. Presented at the 53^rd ASH Annual Meeting and Exposition. San Diego, CA, December 10-13, 2011. Abstract 476.