by Caspian Hartwell - 6 Comments

For decades, leukemia and lymphoma were treated with the same blunt tool: chemotherapy. It killed fast-growing cells-cancerous and healthy alike. Patients lost hair, fought nausea, and spent weeks in hospitals just to survive. But since 2001, when imatinib became the first targeted drug approved for chronic myeloid leukemia, everything changed. Today, we don’t just attack cancer-we outsmart it. Targeted therapies and cellular therapies are now reshaping survival, turning once-fatal diagnoses into manageable conditions-or even cures.

What Are Targeted Therapies, Really?

Targeted therapies are like precision keys that fit only one lock: the exact molecular flaw driving a cancer’s growth. Unlike chemo, which burns through the whole body, these drugs zero in on specific proteins or signals cancer cells depend on. For example, in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), two closely related diseases, the BTK protein acts like a fuel line for cancer cells. Drugs like ibrutinib and acalabrutinib block BTK, starving the cancer of its signal to multiply. Patients take them as pills-once a day, at home. No IVs. No hospital stays. Just a bottle and a routine.

Another key player is venetoclax, which targets BCL-2, a protein that helps cancer cells avoid death. By flipping this survival switch, venetoclax forces malignant cells to self-destruct. Used with obinutuzumab or ibrutinib, it can deliver deep remissions in just 12 to 24 months. That’s a fixed-duration treatment-meaning patients stop after a set time, rather than taking pills for life. For many, this means no more daily medication, fewer side effects, and a real shot at long-term control.

Cellular Therapy: Rewiring Your Immune System to Fight Cancer

If targeted therapies are precision tools, cellular therapies are biological superweapons. CAR T-cell therapy takes your own immune cells-T cells-and turns them into living drugs. Here’s how it works: First, your blood is drawn. T cells are separated out. In a lab, scientists add a synthetic receptor-called a chimeric antigen receptor, or CAR-that lets these T cells recognize CD19, a protein found on the surface of most B-cell lymphomas and leukemias. The cells are multiplied, then infused back into you. Once inside, they hunt down cancer cells like guided missiles.

The first CAR T therapy, tisagenlecleucel (Kymriah), was approved in 2017 for kids with acute lymphoblastic leukemia. Today, we have three FDA-approved options: Kymriah, Yescarta (axicabtagene ciloleucel), and Breyanzi (lisocabtagene maraleucel). Each targets CD19, but they use slightly different engineering. Yescarta, for example, showed a 42.6% four-year survival rate in patients with relapsed large B-cell lymphoma after failing other treatments-something nearly unheard of just five years ago.

Newer versions are even more advanced. Gilead’s KITE-363 and KITE-753 are dual-target CAR T therapies. Instead of just attacking CD19, they also target CD20. This reduces the chance of cancer escaping treatment by losing one antigen. Early results show 63.6% complete remission rates in patients who had exhausted all other options. One patient, a 58-year-old with mantle cell lymphoma that had spread after four prior therapies, achieved a complete response after a single infusion of LV20.19 CAR T cells-no signs of disease 18 months later.

Why These Therapies Beat Old-School Chemo

Traditional chemoimmunotherapy for CLL and lymphoma often extended survival by a year or two-but at a high cost. Patients faced bone marrow suppression, infections, fatigue, and long hospital stays. The CLL Society’s 2025 data shows a dramatic shift: in the targeted therapy era, the median time from CLL diagnosis to Richter transformation (a deadly leap into aggressive lymphoma) jumped from 2.2 years to 4.9 years. That’s over two extra years of living with a manageable disease, not a ticking time bomb.

For relapsed or refractory cases, CAR T-cell therapy crushes older salvage chemo regimens. In the ZUMA-7 trial, Yescarta doubled the rate of progression-free survival compared to standard chemo in second-line large B-cell lymphoma. And it’s not just about length-it’s about quality. Patients on targeted therapies often report near-normal energy levels. Many return to work, travel, or even coach their kids’ soccer teams.

But it’s not all perfect. Targeted therapies can stop working. Resistance builds. Patients with del(17p) or TP53 mutations tend to progress faster on BTK inhibitors. That’s why doctors now combine therapies-like venetoclax plus ibrutinib-to delay resistance. And for those who do relapse, CAR T-cell therapy often remains an option.

Transformed T-cell warrior flying through blood vessels targeting cancer cells

The Real Cost: Money, Access, and Toxicity

These breakthroughs come with heavy price tags. A single CAR T-cell treatment costs between $373,000 and $475,000. Even with insurance, out-of-pocket costs can hit $15,000 to $25,000 per month for oral targeted drugs. That’s financial toxicity-a silent crisis. Many elderly patients with comorbidities face tough choices: take the drug and risk bankruptcy, or skip it and face the disease.

And the side effects? They’re serious. CAR T-cell therapy can trigger cytokine release syndrome (CRS)-a storm of immune chemicals that causes high fever, low blood pressure, and organ stress. Neurotoxicity, including confusion, seizures, or trouble speaking, affects 20-40% of patients. These aren’t side effects you manage at home. They require ICU-level care. That’s why CAR T-cell therapy is only offered at certified centers. In the U.S., 89% of NCI-designated cancer centers offer it. But in rural areas or community clinics? Only 32% do.

Targeted drugs aren’t risk-free either. Venetoclax can cause tumor lysis syndrome-when dying cancer cells flood the bloodstream with toxins. That’s why the first few doses are given in the hospital. Ibrutinib can cause bleeding, atrial fibrillation, and high blood pressure. Patients need regular monitoring: blood tests, EKGs, and check-ins with their oncologist.

Who Gets These Therapies-and When?

Not everyone needs them. For newly diagnosed, low-risk CLL, watchful waiting is still standard. But for high-risk patients-those with del(17p), TP53 mutations, or rapid disease progression-targeted therapies are now first-line. CAR T-cell therapy is reserved for those who’ve failed at least two prior treatments. But that’s changing fast.

In 2025, the FDA granted priority review to liso-cel (Breyanzi) for marginal zone lymphoma, with a decision expected by December. Meanwhile, clinical trials are testing CAR T-cell therapy in first-line treatment for aggressive lymphomas. A 2025 ASCO survey found 68% of hematologists believe CAR T-cell therapy will become standard first-line treatment for high-risk patients by 2030.

Doctors are also exploring these therapies in rare forms like primary CNS lymphoma. Early results show promise. Some patients who had no options left-no chemo, no stem cell transplant-have responded to CAR T therapy injected directly into the spinal fluid.

Split image showing patient’s journey from hospital to outdoor freedom

The Future: Smarter, Safer, Earlier

The next wave of therapies is already here. Researchers are developing off-the-shelf CAR T cells-made from donor cells, not your own. That could cut manufacturing time from 3-5 weeks to days. There are also “armored” CAR T cells with added immune boosters, and CAR NK cells (natural killer cells) that may be safer and easier to store.

Manufacturers are also trying to reduce toxicity. Newer CAR designs include safety switches-genes that can be turned off with a simple pill if side effects get too severe. Some trials are testing lower doses or split infusions to prevent CRS. One study showed that giving CAR T cells in two smaller doses, instead of one big one, cut severe side effects by half.

And the data keeps improving. Real-world outcomes now match clinical trial results. A 2025 report from the Gene, Cell, & RNA Therapy Landscape showed 33 new non-genetically modified cell therapy trials launched in Q2 alone-most targeting solid tumors. That means the tools built for blood cancers are now being adapted for breast, lung, and pancreatic cancers.

What This Means for Patients

If you or someone you love has leukemia or lymphoma, here’s the reality: You have more options than ever. But you also need to be proactive. Ask your oncologist: “Is my cancer being tested for genetic mutations? Am I a candidate for targeted therapy? Should I consider CAR T-cell therapy if this treatment fails?”

Don’t wait until you’ve run out of options. For many, the best time to consider advanced therapy is at diagnosis-not after relapse. If your center doesn’t offer CAR T-cell therapy, ask for a referral. Many manufacturers have patient navigators who help with insurance, travel, and logistics.

And remember: These aren’t magic bullets. But they’re the closest thing we’ve ever had to turning a death sentence into a life with meaning.

What is the difference between targeted therapy and CAR T-cell therapy?

Targeted therapies are oral drugs that block specific proteins cancer cells need to grow, like BTK or BCL-2. They’re taken daily and work systemically. CAR T-cell therapy is a one-time infusion of your own modified immune cells that hunt and kill cancer. It’s more complex, requires hospitalization, and is used when other treatments fail. One is a pill; the other is a living drug.

Are targeted therapies better than chemotherapy?

For most patients with CLL, SLL, and certain lymphomas, yes. Targeted therapies often lead to longer remissions, fewer hospital visits, and less severe side effects than chemo. Studies show patients on BTK inhibitors or venetoclax live longer and report better quality of life. But they’re not always curative, and resistance can develop. Chemo still has a role in aggressive, fast-growing cases or when targeted drugs aren’t available.

Can CAR T-cell therapy cure leukemia or lymphoma?

For some, yes. In patients with relapsed or refractory B-cell acute lymphoblastic leukemia, up to 40% remain in remission five years after CAR T-cell therapy. In aggressive lymphomas like mantle cell lymphoma, complete responses are common-even after multiple relapses. While we don’t yet call it a “cure” for most, many patients live disease-free for years, sometimes decades, with no further treatment needed.

Why is CAR T-cell therapy so expensive?

It’s because it’s personalized medicine. Each treatment is made from your own cells, requiring specialized labs, genetic engineering, strict quality control, and trained staff. The process takes 3-5 weeks and involves multiple steps: leukapheresis, shipping, modification, expansion, and reinfusion. Plus, managing side effects requires ICU-level care. The cost reflects the complexity-not just the drug itself.

What if targeted therapy stops working?

If you develop resistance, your doctor will test for new mutations-like BTK or BCL-2 mutations-and switch you to another targeted drug or consider CAR T-cell therapy. Some patients respond to venetoclax after failing a BTK inhibitor, and vice versa. For those who’ve tried both, clinical trials for next-gen therapies or dual-target CAR T cells may be the best option.

Where can I get CAR T-cell therapy?

CAR T-cell therapy is only available at certified centers-usually large academic hospitals or NCI-designated cancer centers. These sites have the staff, ICU access, and experience to manage side effects. If your local oncologist doesn’t offer it, ask for a referral. Manufacturers like Kite and Novartis also provide patient support programs to help with travel, insurance, and logistics.

These therapies didn’t just extend life-they redefined it. What used to be a terminal diagnosis is now a journey with new milestones: a year without treatment, a child’s graduation, a trip overseas. The science is still evolving, but the message is clear: there’s hope, and it’s no longer a distant dream.